Sgaragli G, Ninci R, Della Corte L, Valoti M, Nardini M, Andreoli V, Moneti G
Drug Metab Dispos. 1986 Mar-Apr;14(2):263-6.
N-Demethylation and dehalogenation of chlorpromazine (CPZ) were compared in six psychotic inpatients and in rats orally treated for 4 weeks with a daily CPZ dose of 5.4 (mean value) and 20 mg X kg-1 body weight, respectively, by measuring drug and metabolite plasma levels by means of a gas-liquid chromatography-nitrogen/phosphorus detector method. In patients the major plasma metabolite was found to be promazine (PZ), as identified by capillary GC-MS analysis. In rats, on the contrary, PZ represented only a small proportion of the compounds detected in plasma. The mean [PZ]/[CPZ] ratio after 4 weeks of treatment was 1.64 in patients and 0.08 in rats. The relative frequency of the N-demethyl metabolites in plasma, however, was similar in the two species. The mean [N-monodemethylated CPZ]/[CPZ] and [N-didemethylated CPZ]/[CPZ] ratios after 4 weeks of treatment were 0.45 and 0.24 in patients and 0.56 and 0.25 in rats, respectively. These findings suggest that dechlorination of CPZ in psychotic patients represents an important metabolic pathway.
通过气液色谱 - 氮/磷检测器法测量药物和代谢物血浆水平，比较了六名精神病住院患者和大鼠中氯丙嗪（CPZ）的N - 去甲基化和脱卤作用。在患者中，分别以每日5.4（平均值）和20 mg·kg⁻¹体重的CPZ剂量口服治疗4周；在大鼠中，也进行了同样为期4周的口服治疗。通过毛细管GC - MS分析鉴定，发现患者血浆中的主要代谢物是丙嗪（PZ）。相反，在大鼠中，PZ仅占血浆中检测到的化合物的一小部分。治疗4周后，患者的平均[PZ]/[CPZ]比值为1.64，大鼠为0.08。然而，两种物种血浆中N - 去甲基代谢物的相对频率相似。治疗4周后，患者的平均[N - 单去甲基化CPZ]/[CPZ]和[N - 双去甲基化CPZ]/[CPZ]比值分别为0.45和0.24，大鼠分别为0.56和0.25。这些发现表明，精神病患者中CPZ的脱氯作用是一条重要的代谢途径。
