Objective To study pharmacokinetics of the main active ingredients(-)Epigallocatechin-3-gallate(EGCG)and(-)Epicatechin-3-gallate(ECG)of tea polyphenols(TP)injection in rats.Methods EGCG and ECG in rat plasma were anal...Objective To study pharmacokinetics of the main active ingredients(-)Epigallocatechin-3-gallate(EGCG)and(-)Epicatechin-3-gallate(ECG)of tea polyphenols(TP)injection in rats.Methods EGCG and ECG in rat plasma were analyzed by reversed-phase HPLC,by which EGCG and ECG were eluted from a Kromasil C18 column with a linear gradient mobile phase consisting of CH3CN-0.1% citric acid at a gradient flow rate of 1.0-1.5 mL·min-1 and monitored at a wavelength of 280 nm.Fifteen rats were randomly divided into 3 groups of 5 animals receiving iv administration of TP injection,formulated with catechins-containing extract from green tea,at doses of 150,100 and 50 mg·kg-1,respectively.Blood samples were collected pre-dosing and 2,5,10,20,40,60,90,120,180,240,300 min postdosing.Aliquots of obtained plasma(200 μL)were cleaned up by liquid-liquid extraction with double volumes of EtoAc and were reconstituted with 100 μL of 10% CH3CN aqueous solution before injecting to chromatograph.Results The time course of EGCG and ECG concentrations in rat plasma decayed in a biexponential fashion.Their iv pharmacokinetics could be described by the two-compartment model and first-order kinetics with t1/2β 112.39-145.20 min and 46.63-61.48 min,Vd 6.28-7.96 L·kg-1 and 0.90-1.22 L·kg-1,CL 0.034-0.044 L·kg-1·min-1 and 0.010-0.015 L·kg-1·min-1 for EGCG and ECG,respectively.Conclusions The EGCG and ECG in plasma of rats administered i.v.TP injection pharmacokinetically behaved with linear kinetics over dose range studied.The two catechin derivatives undergo rapid elimination from rat body.As compared with ECG,EGCG eliminates at a relatively slow rate,and is distributed very widely with a Vd greatly exceeding the volume of total body water,suggesting that EGCG is likely to enter the tissue cells or strongly bind to some tissues to exert its potent antioxidant effects.The aforementioned characteristics of EGCG may be due to its high lipophilicity.展开更多
Objective To study effects of diabetes mellitus(DM)on pharmacokinetics of cephradine(CED)by comparing the difference in pharmacokinetic behaviours of CED between diabetic and normal rats.Methods DM was induced in male...Objective To study effects of diabetes mellitus(DM)on pharmacokinetics of cephradine(CED)by comparing the difference in pharmacokinetic behaviours of CED between diabetic and normal rats.Methods DM was induced in male rats by a single iv injection of alloxan 60 mg·kg-1;rats whose blood glucose was over 16 mmol·L-1 were taken as DM group.The rats were divided into DM group and normal control(CTL)group,which were subdivided into low dose(90 mg·kg-1)and high dose(180 mg·kg-1)subgroups.CED was administered by iv or po routes.Blood samples collected at different time post dosing were analyzed by RP-HPLC to yield CED plasma concentration time course.Chromatographic separation was achieved on a Kromasil C18 column(250×4.6 mm ID,5 μm);mobile phase,consisting of 0.025 mol·L-1 KH2PO4-MeOH-CH3CN(87;6∶7 v/v),was delivered at 1.0 mL·min-1;UV detector was set at 261 nm.The peak area ratio of CED to cephalexin(CEX)as internal standard vs concentraion of CED was used to construct calibration curve.50 μL aliquots of TCA-deproteined plasma samples were injected into chromatograph.Results The methodology validation including specificity,precision,accuracy,recovery,limit of quantitation,linearity,stability,etc.,showed that the HPLC assay developed by us completely met requirements of pharmacokinetic study Both DM and CTL groups showed the two-compartment model for iv dosing and extravascular one-compartment model for po dosing as well as first-order kinetics.However,in iv experiment,DM group,when compared with CTL group,presented a significantly shortened t1/2β and MRT as well as increased CL,reflected by t1/2 β 84-91 vs 116-120 min,MRT 61-70 vs 103-119 min;CL 23-25 vs 18-19 mL·min-1·kg-1(P<0.05);in po experiment,a markedly shorter t1/2 K and tmax as well as greater CL and Cmax in DM group than in CTL group were found;meanwhile,DM rats suffered from remarkably increased kidney weight(KW)and KW/BW ratio relative to CTL rats.Conclusions DM pathological status can speed up elimination of CED from body of rats;the compensatory hypertrophy and thereby hyperfunction of kidneys in early-stage diabetics may explain in part at least this accelerated elimanation.展开更多
Objective To compare the pharmacokinetics of Alprazolam after intranasal and intragastic administration in rats and evaluate the practicability of Alprazolam as a nasal drug delivery system.Methods 12 rats were random...Objective To compare the pharmacokinetics of Alprazolam after intranasal and intragastic administration in rats and evaluate the practicability of Alprazolam as a nasal drug delivery system.Methods 12 rats were randomly divided into two groups.The fate of drug in the serum of rats was monitered after intranasal and intragastic administration of Alprazolam 2 mg·kg-1.Serum levels of Alprazolam were determined by reversed-phase HPLC with Diode array detectors(DAD).Chromatographic conditions were adopted with ODS column as solid phase,methanaol-0.02 M ammonium acetate(pH=5.0)(60∶40)as mobile phase at a flow rate of 1.0 mL·min-1.The detection wavelength was 223 nm.The concentration-time data were analyzed using 3P87 program,and the pharmacokinetic parameters were compared by t-test.Results The pharmacokinetic characteristics were fit to two and one compartment opened model after intranasal and intragastic administration of Alprazolam,respectively.The drug absorption was quicker and the serum concentrations of Alprazolam was significantly higher in rats after intranasal administration group than that intragastic administration group(P<0.05).The eliminate parameters between the two groups were no significant difference(P>0.05).Means of pharmacokinetic parameters in intranasal and intragastic groups were:Ka 37.35±22.98 vs 11.57±12.47 h-1(P<0.05),t1/2ka0.025±0.013 vs 0.156±0.122 h(P<0.05),β(Ke)0.3131±0.1194 vs 0.3091±0.1216 h-1(P>0.05),t1/2β(t1/2Ke)2.51±0.99 vs 2.54±0.97 h(P>0.05),tmax 0.156±0.069 vs 0.618±0.414 h(P<0.01),Cmax 353.11±96.30 vs 62.09±35.08 μg·L-1(P<0.01),AUC 1111.6±473.2 vs 274.1±185.3 μg·L-1·h(P<0.01).Conclusions Alprazolam was absorbed quickly in rats after intranasal administration.And the serum concentration and bioavailability can be significantly increased after intranasal administration,which may be an effective preparation as nasal drug delivery system.展开更多
A sensitive,specific and rapid high-performance liquid chromatography-electronic spray ionization-tandem mass spectrometric method was developed and validated for the determination of 7,4'-dihydroxylflavone(7,4...A sensitive,specific and rapid high-performance liquid chromatography-electronic spray ionization-tandem mass spectrometric method was developed and validated for the determination of 7,4'-dihydroxylflavone(7,4'-DHF)in rat plasma.Genistein(internal standard,IS)was added in the collected plasma samples and subsided together by a simple one-step protein precipitation using acetonitrile-methanol(1:1,v/v).Chromatographic separation was performed on an Agilent Zorbax XDB C18 chromatography column and gradient elution with the mobile phase consisting of methanol and 0.1%formic acid was used.The mass spectrometric detection was performed by negative ion electro-spray ionization in multiple selected reactions monitoring(MRM)mode,with the transitions of m/z 253.1→113.0 for 7,4'-DHF and m/z 268.9→158.8 for IS.The calibration curve has liner relationship over the concentration range of 0.1-50.ng/mL(r=0.995.4).The intra-and inter-day precision(RSD%)was less than 10%,and the accuracy(RE%,relative error)ranged from-5.2%to 8.0%.The fully validated method was applied to the pharmacokinetics(PK)of 7,4'-dihydroxylflavone(7,4'-DHF)in rat plasma after oral administration(two doses:15 and 30.mg/kg)and intravenous injection(5.mg/kg).The result showed that Tmax and Cmax was 1.33±0.29.h and 0.12±0.02.ng/mL(15.mg/kg),and 1.17±0.29.h and 0.17±0.04.ng/mL(30.mg/kg),respectively.The bioavailability was 0.078%(15.mg/kg)and 0.070%(30.mg/kg),respectively.展开更多
In this paper, a microcomputer program package for pharmacokinetics and biopharmaceutics (PKBP) was presented. This package is applicable to various calculations for pharmacokinetics and biopharmaceutics. Some mathema...In this paper, a microcomputer program package for pharmacokinetics and biopharmaceutics (PKBP) was presented. This package is applicable to various calculations for pharmacokinetics and biopharmaceutics. Some mathematical models and computing methods were developed. It has been used over 200 users.展开更多
Solid phase exchange radioiodination method was used to label the compound.Pharmacokinetics was studied in rats and the data were dealt with by computer. The results indicate that the compound would be a potential myo...Solid phase exchange radioiodination method was used to label the compound.Pharmacokinetics was studied in rats and the data were dealt with by computer. The results indicate that the compound would be a potential myocardial imaging agent.展开更多
Objective: To investigate the in vitro antimicrobial activity of panipenem/betamipron to common clinical isolates, determine its pharmacokinetics in patients with pulmonary infection and evaluate its effectiveness and...Objective: To investigate the in vitro antimicrobial activity of panipenem/betamipron to common clinical isolates, determine its pharmacokinetics in patients with pulmonary infection and evaluate its effectiveness and safety in treatment of pulmonary infection. Methods: (1) The minimal inhibition concentrations of panipenem/betamipron were determined in 247 clinical isolates by agar dilution method. The minimal bactericidal concentrations of panipenem/betamipron for some clinical isolates were also determined. (2) Twenty cases of pulmonary infection were treated with intravenous dripping of panipenem/betamipron at 500/500 mg every 12 h for 3-7 d. Panipenem/betamipron concentration in the plasma was consecutively measured, and bacterial culture was conducted and the efficacy was evaluated. Results: (1) The in vitro antimicrobial activity of panipenem/betamipron was almost the same as that of panipenem, indicating that panipenem played the major role in antimicrobial reaction. Panipenem/betamipron had a strong antimicrobial activity against Staphylococcus aureus including methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, β-Streptococcus hemolytic, Streptococcus pneumonia, micrococcus, Escherichia coli and Klebsiea pneumonia. The drug also showed a potent effect against Haemophilus influenzae,Enterobacter cloacae, Proteus and Pseudomonas aeruginosa (2) The peak value of panipenem/betamipron in plasma was (30.25±5.43) mg/L and the level decreased to (0.66±0.34) mg/L 6 h later. The half-life of distribution and elimination of panipenem in the plasma was (0.34±0.18) h and (1.42±0.31) h, respectively. (3) The eradication rate of bacteria was 77.8% and the effective healing rate was 75%. No adverse drug reaction was found. Conclusion: Panipenem/betamipron has a strong antimicrobial activity against clinical isolates and is effective and safe for treatment of pulmonary infection.展开更多
Objective To evaluate the pharmacokinetics(PK)properties of extended release formulations of buspirone hydrochloride in Beagle dogs.Methods A randomized,two period,two treatment,two sequence crossover bioequivalence s...Objective To evaluate the pharmacokinetics(PK)properties of extended release formulations of buspirone hydrochloride in Beagle dogs.Methods A randomized,two period,two treatment,two sequence crossover bioequivalence study was designed;six healthy Beagle dogs were randomly divided into two groups,each group was orally given buspirone tablets or buspirone extended capsule containing 15 mg buspirone hydrochloride.Blood samples(about 1 mL)were collected in heparinized tubes before dosing and at 0.33,0.67,1,2,3,4,6,8,10,12,18,24 h after administration,and were then immediately centrifuged at 3000 rpm for 15 min.The pharmacokinetics(PK)properties of the drugs were evaluated using the liquid chromatographic-tandem mass spectrometric(LC-MS/MS)method.Results The mean tmax was 4.7,0.8 h and Cmax values was 1.8,6.9 μg·L-1,respectively for the sustained-release test(capsule)and reference formulation(tablet).When compared to the tablets,the residence time of the sustained capsules was dramatically prolonged and Cmax was reduced(P<0.01).The initial release speed was slow and stable.The bioavailability was similar to the common tablets.Conclusions The sustained capsule had showed good pharmacokinetics property of sustained-release in the Beagle dogs.展开更多
The safety and toxicity of chemicals given first to animals and finally to humans are generally estimated with a method of safe coefficient, which is scientifically a way lack of grounds. To make a change of the old m...The safety and toxicity of chemicals given first to animals and finally to humans are generally estimated with a method of safe coefficient, which is scientifically a way lack of grounds. To make a change of the old method, we designed a Physiologically Based Pharmacokinetics Medel for the estimate of safety and toxicity of chemicais. As an example,p-nitrophenol sodium (PNP-Na) is used in the research work. Studies of the PNP-Na pharmacokinetics in bodies of rat as well as humans are made, and possibilities of making use of the Model in the estimate of safety and toxicity of chemicals are discussed.展开更多
Higher alcohols are key factors affecting sensory quality and post-drinking comfort of alcoholic beverages. A strategy combining solid-phase extraction and gas chromatography-mass spectrometry(SPE-GC-MS) was establish...Higher alcohols are key factors affecting sensory quality and post-drinking comfort of alcoholic beverages. A strategy combining solid-phase extraction and gas chromatography-mass spectrometry(SPE-GC-MS) was established to analyze the metabolism pattern of higher alcohols in rat plasma after gavage of 4 common alcoholic beverages including huangjiu, baijiu, wine and brandy. 7 mL of dichloromethane was determined as the optimal extraction condition, and 8 higher alcohols were precisely quantified with detection limits of 1.82-11.65 μg/L, recoveries of 89.07%-110.89% and fine repeatability. The fastest absorption and elimination rates of plasma total higher alcohols were observed in baijiu and huangjiu group, respectively, and the highest peak concentration was found in brandy group. Additionally, the metabolic rate of plasma isoamyl alcohol in huangjiu group was faster than that in wine group at the same intragastric administration dosage. This study may provide potential insight for evaluation of alcoholic beverage quality.展开更多
Objective To study the pharmacokinetics of a novel recombinant human granulocyte colonystimulating factor (rhG-CSFa) in rats and to determine the proteolytic rates of rhG-CSFa in the whole blood and serum of rats in v...Objective To study the pharmacokinetics of a novel recombinant human granulocyte colonystimulating factor (rhG-CSFa) in rats and to determine the proteolytic rates of rhG-CSFa in the whole blood and serum of rats in vitro. Methods The pharmacokinetics of rhG-CSFa and conventional (wild type,WT) granulocyte colonystimulating factor (G-CSF) were investigated in Sprague-Dawley rats which received either intravenous or subcutaneous injection of rhG-CSFa or WT G-CSF at three different doses (20,50,or 100 μg/kg). The blood samples of rats were collected at multiple time points (from 0.08 to 12 h) and the concentrations of rhG-CSFa and WT G-CSF in serum were determined with a sandwich enzyme-linked immunosorbent assay (ELISA). For the study of proteolytic rates in vitro,the concentrations of rhG-CSFa or WT G-CSF were determined at 3-minute intervals after addition of the respective drug to rat’s whole blood or serum. Results Pharmacokinetic analysis of serum rhG-CSFa or WT G-CSF levels indicated that,at each dose tested,for either route of drug administration,the area under concentration-time curve values and the maximum serum concentration of rhG-CSFa were higher than those of WT G-CSF,and the serum half life of rhG-CSFa was longer than that of WT G-CSF. Subsequent in vitro whole blood and serum stability study showed that the rates of drug degradation in WT G-CSF were 1.8 folds and 1.5 folds higher than those in rhG-CSFa,respectively. Conclusion rhG-CSFa has better serum and whole blood stability in vitro and higher bioavailability in vivo as compared to WT G-CSF.展开更多
Human aging is a global issue with important implications for current and future incidence and prevalence of health conditions and disability. Cardiac arrhythmias, including atrial fibrillation, sudden cardiac death, ...Human aging is a global issue with important implications for current and future incidence and prevalence of health conditions and disability. Cardiac arrhythmias, including atrial fibrillation, sudden cardiac death, and bradycardia requiring pacemaker placement, all increase exponentially after the age of 60. It is important to distinguish between the normal, physiological consequences of aging on cardiac electrophysiology and the abnormal, pathological alterations. The age-related cardiac changes include ventricular hypertrophy, senile amyloidosis, cardiac valvular degenerative changes and annular calcification, fibrous infiltration of the conduction system, and loss of natural pacemaker cells and these changes could have a profound effect on the development of arrhythmias. The age-related cardiac electrophysiological changes include up- and down-regulation of specific ion channel expression and intmcellular Ca2＋ overload which promote the development of cardiac arrhythmias. As ion channels are the substrates of antiarrhythmic drugs, it follows that the pharmacokinetics and pharmacodynamics of these drugs will also change with age. Aging alters the absorption, distribution, metabolism, and elimination of antiarrhythmic drugs, so liver and kidney function must be monitored to avoid potential adverse drug effects, and antiarrhythmic dosing may need to be adjusted for age. Elderly patients are also more susceptible to the side effects of many antiarrhytbanics, including bradycardia, orthostatic hypotension, urinary retention, and falls. Moreover, the choice of antiarrhythmic drugs in the elderly patient is frequently complicated by the presence of co-morbid conditions and by polypharmacy, and the astute physician must pay careful attention to potential drug-drug interactions. Finally, it is important to remember that the use of antiarrhythmic drugs in elderly patients must be individualized and tailored to each patient＇s physiology, disease processes, and medication regimen.展开更多
AEOL-10150 is a broad-spectrum metalloporphyrin superoxidase dismutase(SOD) mimic specifically designed to neutralize reactive oxygen and nitrogen species. Research has shown that AEOL-10150 is a potent medical counte...AEOL-10150 is a broad-spectrum metalloporphyrin superoxidase dismutase(SOD) mimic specifically designed to neutralize reactive oxygen and nitrogen species. Research has shown that AEOL-10150 is a potent medical countermeasure against national security threats including sulfur mustard(SM), nerve agent exposure and radiation pneumonitis following a radiological/nuclear incident sufficient to cause acute radiation syndrome(ARS). AEOL-10150 performed well in animal safety studies, and two completed phase 1 safety studies in patients demonstrated that the drug was safe and well tolerated, indicating that AEOL-10150 has potential as a new catalytic antioxidant drug. In this article, we review improvements in AEOL-10150 in preclinical pharmacodynamic studies, especially regarding anti-SM,chlorine gas and radiation exposure studies.展开更多
1 Introduction Although older adults are generally among the highest users of cardiovascular medications, they are typically underrepresented or excluded from most efficacy and safety trials. Drug developers are usual...1 Introduction Although older adults are generally among the highest users of cardiovascular medications, they are typically underrepresented or excluded from most efficacy and safety trials. Drug developers are usually reluctant to include many senior adults in randomized controlled clinical trials in part due to their high prevalence of multiple comorbidities, frailty, and polypharmacy; and to age-related pharmacokinetic and pharmacodynamic complexities. Consequently, there is often insufficient high quality evidence-based data to inform pharmacologic management of common cardiovascular conditions on older adults. In the absence of data, clinicians often rely on conceptual principles regarding metabolism and drug-drug interactions to minimize adverse drug events, but this is often not well-substantiated or standardized. A related challenge is poor cardiovascular medication adherence among older adults, and its detrimental impact on their health outcomes. In this brief review we highlight some aspects of these topics.展开更多
The concentrations of Ti and Ca, P, K, Fe, Cu and Zn in blood samples were determined by PIXE after a single intravenous and a single oral dosing with titanium- ascorbate (Ti- Vc) in Wister rats. Following the intrave...The concentrations of Ti and Ca, P, K, Fe, Cu and Zn in blood samples were determined by PIXE after a single intravenous and a single oral dosing with titanium- ascorbate (Ti- Vc) in Wister rats. Following the intravenous injection with 50 mg Ti- Vc/kg body weight, the absorption, distribution and clearance in blood could be described by an exponential equation of three terms. After gavaged with 500 mg Ti-Vc/kg body weight, at 1.5 h the content of Ti reached the highest level. The concentration of Ca was increasing, with the absorption, distribution and clearance of Ti in blood. The contents of Fe and K were decreasing. And the contents of Cu and Zn were significantly fluctuating. The effect of Ti on animal growth could be explained by the fact that Ti- Vc supplementation could promote the absorption of Ca.展开更多
文摘Objective To study pharmacokinetics of the main active ingredients(-)Epigallocatechin-3-gallate(EGCG)and(-)Epicatechin-3-gallate(ECG)of tea polyphenols(TP)injection in rats.Methods EGCG and ECG in rat plasma were analyzed by reversed-phase HPLC,by which EGCG and ECG were eluted from a Kromasil C18 column with a linear gradient mobile phase consisting of CH3CN-0.1% citric acid at a gradient flow rate of 1.0-1.5 mL·min-1 and monitored at a wavelength of 280 nm.Fifteen rats were randomly divided into 3 groups of 5 animals receiving iv administration of TP injection,formulated with catechins-containing extract from green tea,at doses of 150,100 and 50 mg·kg-1,respectively.Blood samples were collected pre-dosing and 2,5,10,20,40,60,90,120,180,240,300 min postdosing.Aliquots of obtained plasma(200 μL)were cleaned up by liquid-liquid extraction with double volumes of EtoAc and were reconstituted with 100 μL of 10% CH3CN aqueous solution before injecting to chromatograph.Results The time course of EGCG and ECG concentrations in rat plasma decayed in a biexponential fashion.Their iv pharmacokinetics could be described by the two-compartment model and first-order kinetics with t1/2β 112.39-145.20 min and 46.63-61.48 min,Vd 6.28-7.96 L·kg-1 and 0.90-1.22 L·kg-1,CL 0.034-0.044 L·kg-1·min-1 and 0.010-0.015 L·kg-1·min-1 for EGCG and ECG,respectively.Conclusions The EGCG and ECG in plasma of rats administered i.v.TP injection pharmacokinetically behaved with linear kinetics over dose range studied.The two catechin derivatives undergo rapid elimination from rat body.As compared with ECG,EGCG eliminates at a relatively slow rate,and is distributed very widely with a Vd greatly exceeding the volume of total body water,suggesting that EGCG is likely to enter the tissue cells or strongly bind to some tissues to exert its potent antioxidant effects.The aforementioned characteristics of EGCG may be due to its high lipophilicity.
文摘Objective To study effects of diabetes mellitus(DM)on pharmacokinetics of cephradine(CED)by comparing the difference in pharmacokinetic behaviours of CED between diabetic and normal rats.Methods DM was induced in male rats by a single iv injection of alloxan 60 mg·kg-1;rats whose blood glucose was over 16 mmol·L-1 were taken as DM group.The rats were divided into DM group and normal control(CTL)group,which were subdivided into low dose(90 mg·kg-1)and high dose(180 mg·kg-1)subgroups.CED was administered by iv or po routes.Blood samples collected at different time post dosing were analyzed by RP-HPLC to yield CED plasma concentration time course.Chromatographic separation was achieved on a Kromasil C18 column(250×4.6 mm ID,5 μm);mobile phase,consisting of 0.025 mol·L-1 KH2PO4-MeOH-CH3CN(87;6∶7 v/v),was delivered at 1.0 mL·min-1;UV detector was set at 261 nm.The peak area ratio of CED to cephalexin(CEX)as internal standard vs concentraion of CED was used to construct calibration curve.50 μL aliquots of TCA-deproteined plasma samples were injected into chromatograph.Results The methodology validation including specificity,precision,accuracy,recovery,limit of quantitation,linearity,stability,etc.,showed that the HPLC assay developed by us completely met requirements of pharmacokinetic study Both DM and CTL groups showed the two-compartment model for iv dosing and extravascular one-compartment model for po dosing as well as first-order kinetics.However,in iv experiment,DM group,when compared with CTL group,presented a significantly shortened t1/2β and MRT as well as increased CL,reflected by t1/2 β 84-91 vs 116-120 min,MRT 61-70 vs 103-119 min;CL 23-25 vs 18-19 mL·min-1·kg-1(P<0.05);in po experiment,a markedly shorter t1/2 K and tmax as well as greater CL and Cmax in DM group than in CTL group were found;meanwhile,DM rats suffered from remarkably increased kidney weight(KW)and KW/BW ratio relative to CTL rats.Conclusions DM pathological status can speed up elimination of CED from body of rats;the compensatory hypertrophy and thereby hyperfunction of kidneys in early-stage diabetics may explain in part at least this accelerated elimanation.
文摘Objective To compare the pharmacokinetics of Alprazolam after intranasal and intragastic administration in rats and evaluate the practicability of Alprazolam as a nasal drug delivery system.Methods 12 rats were randomly divided into two groups.The fate of drug in the serum of rats was monitered after intranasal and intragastic administration of Alprazolam 2 mg·kg-1.Serum levels of Alprazolam were determined by reversed-phase HPLC with Diode array detectors(DAD).Chromatographic conditions were adopted with ODS column as solid phase,methanaol-0.02 M ammonium acetate(pH=5.0)(60∶40)as mobile phase at a flow rate of 1.0 mL·min-1.The detection wavelength was 223 nm.The concentration-time data were analyzed using 3P87 program,and the pharmacokinetic parameters were compared by t-test.Results The pharmacokinetic characteristics were fit to two and one compartment opened model after intranasal and intragastic administration of Alprazolam,respectively.The drug absorption was quicker and the serum concentrations of Alprazolam was significantly higher in rats after intranasal administration group than that intragastic administration group(P<0.05).The eliminate parameters between the two groups were no significant difference(P>0.05).Means of pharmacokinetic parameters in intranasal and intragastic groups were:Ka 37.35±22.98 vs 11.57±12.47 h-1(P<0.05),t1/2ka0.025±0.013 vs 0.156±0.122 h(P<0.05),β(Ke)0.3131±0.1194 vs 0.3091±0.1216 h-1(P>0.05),t1/2β(t1/2Ke)2.51±0.99 vs 2.54±0.97 h(P>0.05),tmax 0.156±0.069 vs 0.618±0.414 h(P<0.01),Cmax 353.11±96.30 vs 62.09±35.08 μg·L-1(P<0.01),AUC 1111.6±473.2 vs 274.1±185.3 μg·L-1·h(P<0.01).Conclusions Alprazolam was absorbed quickly in rats after intranasal administration.And the serum concentration and bioavailability can be significantly increased after intranasal administration,which may be an effective preparation as nasal drug delivery system.
基金National Natural Science Foundation of China(81573693)。
文摘A sensitive,specific and rapid high-performance liquid chromatography-electronic spray ionization-tandem mass spectrometric method was developed and validated for the determination of 7,4'-dihydroxylflavone(7,4'-DHF)in rat plasma.Genistein(internal standard,IS)was added in the collected plasma samples and subsided together by a simple one-step protein precipitation using acetonitrile-methanol(1:1,v/v).Chromatographic separation was performed on an Agilent Zorbax XDB C18 chromatography column and gradient elution with the mobile phase consisting of methanol and 0.1%formic acid was used.The mass spectrometric detection was performed by negative ion electro-spray ionization in multiple selected reactions monitoring(MRM)mode,with the transitions of m/z 253.1→113.0 for 7,4'-DHF and m/z 268.9→158.8 for IS.The calibration curve has liner relationship over the concentration range of 0.1-50.ng/mL(r=0.995.4).The intra-and inter-day precision(RSD%)was less than 10%,and the accuracy(RE%,relative error)ranged from-5.2%to 8.0%.The fully validated method was applied to the pharmacokinetics(PK)of 7,4'-dihydroxylflavone(7,4'-DHF)in rat plasma after oral administration(two doses:15 and 30.mg/kg)and intravenous injection(5.mg/kg).The result showed that Tmax and Cmax was 1.33±0.29.h and 0.12±0.02.ng/mL(15.mg/kg),and 1.17±0.29.h and 0.17±0.04.ng/mL(30.mg/kg),respectively.The bioavailability was 0.078%(15.mg/kg)and 0.070%(30.mg/kg),respectively.
文摘In this paper, a microcomputer program package for pharmacokinetics and biopharmaceutics (PKBP) was presented. This package is applicable to various calculations for pharmacokinetics and biopharmaceutics. Some mathematical models and computing methods were developed. It has been used over 200 users.
文摘Solid phase exchange radioiodination method was used to label the compound.Pharmacokinetics was studied in rats and the data were dealt with by computer. The results indicate that the compound would be a potential myocardial imaging agent.
文摘Objective: To investigate the in vitro antimicrobial activity of panipenem/betamipron to common clinical isolates, determine its pharmacokinetics in patients with pulmonary infection and evaluate its effectiveness and safety in treatment of pulmonary infection. Methods: (1) The minimal inhibition concentrations of panipenem/betamipron were determined in 247 clinical isolates by agar dilution method. The minimal bactericidal concentrations of panipenem/betamipron for some clinical isolates were also determined. (2) Twenty cases of pulmonary infection were treated with intravenous dripping of panipenem/betamipron at 500/500 mg every 12 h for 3-7 d. Panipenem/betamipron concentration in the plasma was consecutively measured, and bacterial culture was conducted and the efficacy was evaluated. Results: (1) The in vitro antimicrobial activity of panipenem/betamipron was almost the same as that of panipenem, indicating that panipenem played the major role in antimicrobial reaction. Panipenem/betamipron had a strong antimicrobial activity against Staphylococcus aureus including methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, β-Streptococcus hemolytic, Streptococcus pneumonia, micrococcus, Escherichia coli and Klebsiea pneumonia. The drug also showed a potent effect against Haemophilus influenzae,Enterobacter cloacae, Proteus and Pseudomonas aeruginosa (2) The peak value of panipenem/betamipron in plasma was (30.25±5.43) mg/L and the level decreased to (0.66±0.34) mg/L 6 h later. The half-life of distribution and elimination of panipenem in the plasma was (0.34±0.18) h and (1.42±0.31) h, respectively. (3) The eradication rate of bacteria was 77.8% and the effective healing rate was 75%. No adverse drug reaction was found. Conclusion: Panipenem/betamipron has a strong antimicrobial activity against clinical isolates and is effective and safe for treatment of pulmonary infection.
文摘Objective To evaluate the pharmacokinetics(PK)properties of extended release formulations of buspirone hydrochloride in Beagle dogs.Methods A randomized,two period,two treatment,two sequence crossover bioequivalence study was designed;six healthy Beagle dogs were randomly divided into two groups,each group was orally given buspirone tablets or buspirone extended capsule containing 15 mg buspirone hydrochloride.Blood samples(about 1 mL)were collected in heparinized tubes before dosing and at 0.33,0.67,1,2,3,4,6,8,10,12,18,24 h after administration,and were then immediately centrifuged at 3000 rpm for 15 min.The pharmacokinetics(PK)properties of the drugs were evaluated using the liquid chromatographic-tandem mass spectrometric(LC-MS/MS)method.Results The mean tmax was 4.7,0.8 h and Cmax values was 1.8,6.9 μg·L-1,respectively for the sustained-release test(capsule)and reference formulation(tablet).When compared to the tablets,the residence time of the sustained capsules was dramatically prolonged and Cmax was reduced(P<0.01).The initial release speed was slow and stable.The bioavailability was similar to the common tablets.Conclusions The sustained capsule had showed good pharmacokinetics property of sustained-release in the Beagle dogs.
文摘The safety and toxicity of chemicals given first to animals and finally to humans are generally estimated with a method of safe coefficient, which is scientifically a way lack of grounds. To make a change of the old method, we designed a Physiologically Based Pharmacokinetics Medel for the estimate of safety and toxicity of chemicais. As an example,p-nitrophenol sodium (PNP-Na) is used in the research work. Studies of the PNP-Na pharmacokinetics in bodies of rat as well as humans are made, and possibilities of making use of the Model in the estimate of safety and toxicity of chemicals are discussed.
基金supported by the National Natural Science Foundation of China(22138004 and 32001828).
文摘Higher alcohols are key factors affecting sensory quality and post-drinking comfort of alcoholic beverages. A strategy combining solid-phase extraction and gas chromatography-mass spectrometry(SPE-GC-MS) was established to analyze the metabolism pattern of higher alcohols in rat plasma after gavage of 4 common alcoholic beverages including huangjiu, baijiu, wine and brandy. 7 mL of dichloromethane was determined as the optimal extraction condition, and 8 higher alcohols were precisely quantified with detection limits of 1.82-11.65 μg/L, recoveries of 89.07%-110.89% and fine repeatability. The fastest absorption and elimination rates of plasma total higher alcohols were observed in baijiu and huangjiu group, respectively, and the highest peak concentration was found in brandy group. Additionally, the metabolic rate of plasma isoamyl alcohol in huangjiu group was faster than that in wine group at the same intragastric administration dosage. This study may provide potential insight for evaluation of alcoholic beverage quality.
基金Supported by State Scientific Key Projects for New Drug Research and Development (2009ZX09102-250)High-tech Research Project for Medicine and Pharmacology of Jiangsu province (BG20070605)
文摘Objective To study the pharmacokinetics of a novel recombinant human granulocyte colonystimulating factor (rhG-CSFa) in rats and to determine the proteolytic rates of rhG-CSFa in the whole blood and serum of rats in vitro. Methods The pharmacokinetics of rhG-CSFa and conventional (wild type,WT) granulocyte colonystimulating factor (G-CSF) were investigated in Sprague-Dawley rats which received either intravenous or subcutaneous injection of rhG-CSFa or WT G-CSF at three different doses (20,50,or 100 μg/kg). The blood samples of rats were collected at multiple time points (from 0.08 to 12 h) and the concentrations of rhG-CSFa and WT G-CSF in serum were determined with a sandwich enzyme-linked immunosorbent assay (ELISA). For the study of proteolytic rates in vitro,the concentrations of rhG-CSFa or WT G-CSF were determined at 3-minute intervals after addition of the respective drug to rat’s whole blood or serum. Results Pharmacokinetic analysis of serum rhG-CSFa or WT G-CSF levels indicated that,at each dose tested,for either route of drug administration,the area under concentration-time curve values and the maximum serum concentration of rhG-CSFa were higher than those of WT G-CSF,and the serum half life of rhG-CSFa was longer than that of WT G-CSF. Subsequent in vitro whole blood and serum stability study showed that the rates of drug degradation in WT G-CSF were 1.8 folds and 1.5 folds higher than those in rhG-CSFa,respectively. Conclusion rhG-CSFa has better serum and whole blood stability in vitro and higher bioavailability in vivo as compared to WT G-CSF.
文摘Human aging is a global issue with important implications for current and future incidence and prevalence of health conditions and disability. Cardiac arrhythmias, including atrial fibrillation, sudden cardiac death, and bradycardia requiring pacemaker placement, all increase exponentially after the age of 60. It is important to distinguish between the normal, physiological consequences of aging on cardiac electrophysiology and the abnormal, pathological alterations. The age-related cardiac changes include ventricular hypertrophy, senile amyloidosis, cardiac valvular degenerative changes and annular calcification, fibrous infiltration of the conduction system, and loss of natural pacemaker cells and these changes could have a profound effect on the development of arrhythmias. The age-related cardiac electrophysiological changes include up- and down-regulation of specific ion channel expression and intmcellular Ca2＋ overload which promote the development of cardiac arrhythmias. As ion channels are the substrates of antiarrhythmic drugs, it follows that the pharmacokinetics and pharmacodynamics of these drugs will also change with age. Aging alters the absorption, distribution, metabolism, and elimination of antiarrhythmic drugs, so liver and kidney function must be monitored to avoid potential adverse drug effects, and antiarrhythmic dosing may need to be adjusted for age. Elderly patients are also more susceptible to the side effects of many antiarrhytbanics, including bradycardia, orthostatic hypotension, urinary retention, and falls. Moreover, the choice of antiarrhythmic drugs in the elderly patient is frequently complicated by the presence of co-morbid conditions and by polypharmacy, and the astute physician must pay careful attention to potential drug-drug interactions. Finally, it is important to remember that the use of antiarrhythmic drugs in elderly patients must be individualized and tailored to each patient＇s physiology, disease processes, and medication regimen.
基金supported by the Grants from Chinese Scientific and Technological Major Special Project(2015ZX09J15104002–002,2016ZX09J16104)
文摘AEOL-10150 is a broad-spectrum metalloporphyrin superoxidase dismutase(SOD) mimic specifically designed to neutralize reactive oxygen and nitrogen species. Research has shown that AEOL-10150 is a potent medical countermeasure against national security threats including sulfur mustard(SM), nerve agent exposure and radiation pneumonitis following a radiological/nuclear incident sufficient to cause acute radiation syndrome(ARS). AEOL-10150 performed well in animal safety studies, and two completed phase 1 safety studies in patients demonstrated that the drug was safe and well tolerated, indicating that AEOL-10150 has potential as a new catalytic antioxidant drug. In this article, we review improvements in AEOL-10150 in preclinical pharmacodynamic studies, especially regarding anti-SM,chlorine gas and radiation exposure studies.
文摘1 Introduction Although older adults are generally among the highest users of cardiovascular medications, they are typically underrepresented or excluded from most efficacy and safety trials. Drug developers are usually reluctant to include many senior adults in randomized controlled clinical trials in part due to their high prevalence of multiple comorbidities, frailty, and polypharmacy; and to age-related pharmacokinetic and pharmacodynamic complexities. Consequently, there is often insufficient high quality evidence-based data to inform pharmacologic management of common cardiovascular conditions on older adults. In the absence of data, clinicians often rely on conceptual principles regarding metabolism and drug-drug interactions to minimize adverse drug events, but this is often not well-substantiated or standardized. A related challenge is poor cardiovascular medication adherence among older adults, and its detrimental impact on their health outcomes. In this brief review we highlight some aspects of these topics.
基金The Project Supported by National Natural Science Foundation of China
文摘The concentrations of Ti and Ca, P, K, Fe, Cu and Zn in blood samples were determined by PIXE after a single intravenous and a single oral dosing with titanium- ascorbate (Ti- Vc) in Wister rats. Following the intravenous injection with 50 mg Ti- Vc/kg body weight, the absorption, distribution and clearance in blood could be described by an exponential equation of three terms. After gavaged with 500 mg Ti-Vc/kg body weight, at 1.5 h the content of Ti reached the highest level. The concentration of Ca was increasing, with the absorption, distribution and clearance of Ti in blood. The contents of Fe and K were decreasing. And the contents of Cu and Zn were significantly fluctuating. The effect of Ti on animal growth could be explained by the fact that Ti- Vc supplementation could promote the absorption of Ca.
