Eggert Hansen C, Rosted Christensen T, Elley J, Bolvig Hansen L, Kragh-Sorensen P, Larsen N E, Naestoft J, Hvidberg E F
Br J Clin Pharmacol. 1976 Oct;3(5):915-23. doi: 10.1111/j.1365-2125.1976.tb00647.x.
A gas-chromatographic method was used for the study in man of the kinetics of perphenazine (PPZ) and its sulphoxide metabolite (PPZ-SO). Various forms of PPZ administration were applied in eighteen schizophrenic patients and four healthy volunteers. Following an i.v. dose of 5 or 6 mg a considerable fluctuation in the plasma concentration was noted before the exponential elimination phase. The average terminal half-life of PPZ was approximately 9.5 hours. PPZ-SO showed up quickly but in low concentrations. After an oral dose of 6 mg no PPZ was detected in plasma and PPZ-SO only as traces. During continuous oral medication, 12 mg three times daily, a low systemic availability and a high PPZ-SO/PPZ ratio was found suggesting a marked first pass effect. PPZ-enanthate given i.m. fortnightly resulted in PPZ-levels comparable to those seen after continuous oral medication, but PPZ-SO concentration were much lower. No accumulation was observed. The systemic clearance rate (average approximately 100 1/h) was the same after PPZ-enanthate i.m. and PPZ i.v., but varied three-fold individually. Side effects were mostly, but not always, registered concomitant with high plasma levels of PPZ.
采用气相色谱法研究奋乃静（PPZ）及其亚砜代谢物（PPZ-SO）在人体中的动力学。对18例精神分裂症患者和4名健康志愿者采用了多种PPZ给药方式。静脉注射5或6毫克剂量后，在指数消除期之前血浆浓度出现相当大的波动。PPZ的平均终末半衰期约为9.5小时。PPZ-SO迅速出现但浓度较低。口服6毫克剂量后，血浆中未检测到PPZ，仅检测到痕量的PPZ-SO。在连续口服给药期间，每日3次，每次12毫克，发现全身可用性低且PPZ-SO/PPZ比值高，提示有明显的首过效应。每两周肌肉注射一次庚酸奋乃静，其PPZ水平与连续口服给药后相当，但PPZ-SO浓度低得多。未观察到蓄积现象。肌肉注射庚酸奋乃静和静脉注射PPZ后的全身清除率（平均约100升/小时）相同，但个体差异为三倍。副作用大多（但并非总是）与血浆中高浓度的PPZ同时出现。
