摘要
目的探讨反映P450酶的亚型1AZ（CYP1A2）活性的咖啡因试验与精神分裂症患者血清氯氮平稳态浓度的相关性。方法16例精神分裂症患者单一口服氯氮平，剂量范围300－450mg/d，剂量固定＞1周，早晨服药前采血。在口服氯氟平采血的同日给予单剂咖啡因150mg口服，第5小时未采血。结果16例精神分裂症患者中，反映CYP1AZ活性的血清次黄嘌吟／咖啡因的比值与去甲氯氮平和氯氟平浓度的比值显著相关（r＝0.7953，P＜0．01），与氯氮平浓度和剂量的比值之间存在负相关（r＝－0．5434，P＜0．05），与去甲氯氮平浓度和氨氮平剂量的比值之间不相关（r＝0．3923，P＞0．05）。结论CYP1A2活性与去甲氯氮平的生成率及氯氮平代谢清除后的单位剩余量之间分别存在相关和负相关，CYP1A2在体内氯氮平去甲基代谢中起主要作用。
Objective The aim of the present Study was to investigate the relationship betwen CYP1A2activity and serum clozapine steady-state concentration in schizophrenics. Methods Sixteen patients (8 male, 8female) entered in the study. The subjects received a fixed dosage of clozapine alone (dose range, 300~450 mgper day) for more than one week. Venous blood samgles were collected in the morning of caffeine test, before administration of clozapine. At 09:30 of the same day, a single oral 150 mg dose of caffeine was given to the subjectsand the blood samples were drawn again after 6-hour of caffeine intake. Results In 16 patients, CYP1A2 activityindex (serum paraxanthin/caffeine ratio) was positively correlated with clozapine demethylation index (serumdesmethylclozapine/clozapine ratio, r = 0. 795 3, P＜0.01), and was negatively correlated with serum concentration/oral dose of clozapine ratio (r=-0.543 4, P＜0.05), respectively. But CYP1A2 activity index was notrelated with the ratio of serum desmethylclozapine concentration to clozapine oral dose (r=0. 392 3, P＞0. 05).Conclusions It is suggested that CYP1A2 may play a major role in the clozapine demethylated metaboism inschizophrenic patients.
出处
《中华精神科杂志》
CAS
CSCD
1999年第2期76-79,共4页
Chinese Journal of Psychiatry
关键词
精神分裂症
氯氮平
咖啡因
药代动力学
治疗
Schizophrenia Clozapine Caffeine Cytochrome P-450 Pharmacokinetics
