Ishizaki T, Chiba K, Saito M, Kobayashi K, Iizuka R
J Clin Psychopharmacol. 1984 Oct;4(5):254-61.
The steady state trough concentrations (Cmin) and pharmacokinetics of valproic acid were investigated in schizophrenic patients during the treatment of valproic acid, 200 mg, twice daily and after the one dose of 400 mg, respectively, with and without haloperidol (6 to 10 mg/day, N = 6) or chlorpromazine (100 to 300 mg/day, N = 6). Four to 5 Cmin were monitored just before the morning valproic acid dose for 3 to 4 days preceding the kinetic study. The overall Cmin of valproic acid with chlorpromazine (33.2 +/- 1.7 micrograms/ml, N = 25) was significantly (p less than 0.01) greater than without (27.1 +/- 1.4 micrograms/ml, N = 25). The majority of the mean valproic acid concentrations observed after the 400-mg dose were significantly (p less than 0.05 to 0.01) greater during the chlorpromazine treatment as compared to those without the phenothiazine. The mean t1/2 was shortened from 15.4 +/- 1.4 to 13.5 +/- 1.2 hours (p less than 0.05) with a comparable increase in the clearance from 7.18 +/- 0.38 to 8.32 +/- 0.34 ml/hour/kg (p less than 0.01) after the discontinuation of chlorpromazine. All the patients revealed an increase in the valproic acid clearance after the chlorpromazine therapy was discontinued. When viewed overall, such a trend as found in the chlorpromazine group was not observed in the haloperidol group. The results suggest that chlorpromazine, but not haloperidol, inhibits the metabolism of valproic acid. However, the clinical significance of the interaction awaits future study.
在精神分裂症患者中，分别研究了丙戊酸每日两次、每次200mg治疗期间及单次服用400mg后，联用和不联用氟哌啶醇（6至10mg/天，N = 6）或氯丙嗪（100至300mg/天，N = 6）时丙戊酸的稳态谷浓度（Cmin）和药代动力学。在进行动力学研究前3至4天，于每日早晨服用丙戊酸剂量前监测4至5次Cmin。联用氯丙嗪时丙戊酸的总体Cmin（33.2±1.7μg/ml，N = 25）显著（p＜0.01）高于未联用者（27.1±1.4μg/ml，N = 25）。与未使用吩噻嗪类药物相比，氯丙嗪治疗期间400mg剂量后观察到的大多数丙戊酸平均浓度显著（p＜0.05至0.01）更高。停用氯丙嗪后，平均t1/2从15.4±1.4小时缩短至13.5±1.2小时（p＜0.05），清除率相应增加，从7.18±0.38ml/小时/千克增至8.32±0.34ml/小时/千克（p＜0.01）。所有患者在停用氯丙嗪治疗后丙戊酸清除率均增加。总体来看，氟哌啶醇组未观察到氯丙嗪组中发现的这种趋势。结果表明，氯丙嗪而非氟哌啶醇抑制丙戊酸的代谢。然而，这种相互作用的临床意义有待未来研究。
