氯氮平药代动力学特点与实施个体化给药方案的评估

THE PHARMACOKINETIC CHARACTERS OF CLOZAPINE AND EVALUATION ON REALIZATION OF ITS INDIVIDUAL REGIMEN

目的 :探讨氯氮平药代动力学特点与应用药代动力学参数计算给药方法的可行性。方法 :30例观察组患者空腹 12h后 ,一次口服氯氮平 75mg。给药后于 0 .5 ,2 ,5 ,8,12 ,2 4,36h取血测定血药浓度 ,求得氯氮平的药代动力学参数 ,并依据药代动力学参数计算给药 ;对照组 30例按照临床经验法给药。治疗后 1月再进行血药浓度测定 ,并于治疗前、治疗后 1,2 ,3个月进行BPRS ,SANS ,TESS测定。结果 :精神分裂症患者吸收相半衰期为 0 .6 8h ,清除相半衰期为 13.0 9h ,清除率为 0 .0 5 7L/h。相同剂量的不同个体峰浓度差异较大 ,最低浓度和最高浓度相差近7倍。观察组BPRS治疗后总分明显降低 (P <0 .0 5 ) ,对照组治疗前后差异不明显。二组SANS治疗前后差异均不明显。观察组TESS总分治疗后明显低于对照组 (P <0 .0 1)。结论 :应用药代动力学参数给药有助于合理用药 ,提高疗效 。

OBJECTIVE:To study the pharmacokinetic characters of clozapine and the feasibility of regimen obtained from calculation of pharmacokinetic parameters. METHODS:In the active group, 30 patients who have been fasted for 12h were treated with a single dose of 75mg clozapine, their plasma drug level were measured at 0.5,2,5,8,12, and 32 h respectively and then they were treated with a regimen calculated from the pharmacokinetic parameters. In the control group, patients were treated with clozapine by routine approach and their plasma drug level were measured after 1 month treatment and the scales of BPRS, SANS, and TESS were evaluated before treatment and 1, 2, and 3 months after treatment .RESULTS:The t 1/2 of absorbtive phase, t 1/2 of clearance phase and clearance rate were 0.68,13.09,and 0.057 L/h respectively . Significant difference in drug peak level has been revealed among patients receiving the same dose of drug and the difference may be as high as 7 folds. The post treatment total BPRS scores in active group were significantly reduced ( P <0.05) but no obvious reduction in control group. No significant difference in pre and post treatment SANS existed in both active and control groups. In active group, the post treatment total TESS scores were significantly lower than that of pre treatment.CONCLUSION:With the help of pharmacokinetic parameters the efficacy, the incidence of side effects and the rational use of antipsychotic agent may be greatly improved.