Bougerol T, Gouezo F, Pok Phak Rop P, Valli M, Durand A, Conquy T, Scotto J C, Viala A
Service Hospitalo-Universitaire de Psychiatrie d'Adultes, Hôpital Sainte-Marguerite.
Encephale. 1990 Jan-Feb;16(1):35-40.
Metapramine (Timaxel) and his three major metabolites (19148 RP, 23669 RP, 19749 RP) have been determined in the plasma of 18 depressed inpatients treated by the antidepressant drug (12 women and 6 men; 7 are smokers and 11 non-smokers). In a steady state, interindividual variability is very important, especially for 23669 RP. No significant correlation exists between normalized doses (mg.kg-1) and normalized plasma concentrations (ng.ml-1/dose mg.kg-1) of metapramine or anyone of its metabolites. The plasma metabolic ratios reveal also important intraindividual and interindividual variability. Two populations of patients seem to exist: extensive metabolizers and relatively poor metabolizers, without apparent clinical consequence because 23669 RP shows an antidepressant activity. Women seem, with equal normalized doses, to exhibit higher plasma levels of unchanged metapramine than men, due to a lower protein-binding rather than to a more active metabolism. In patients who received a poly-medication smoking seems not to induce desmethylation of metapramine. The plasma metabolic ratios, compared by the analysis of variance and the Wilcoxon distribution-free test, are significatively influenced by sex and not by tobacco-smoking.
已对18名接受抗抑郁药物治疗的住院抑郁症患者（12名女性和6名男性；7名吸烟者和11名非吸烟者）的血浆中的甲丙氨酯（替马西泮）及其三种主要代谢物（19148 RP、23669 RP、19749 RP）进行了测定。在稳态下，个体间变异性非常重要，尤其是对于23669 RP。甲丙氨酯或其任何一种代谢物的标准化剂量（mg·kg⁻¹）与标准化血浆浓度（ng·ml⁻¹/剂量mg·kg⁻¹）之间不存在显著相关性。血浆代谢比也显示出重要的个体内和个体间变异性。似乎存在两类患者群体：代谢快者和代谢相对较慢者，由于23669 RP具有抗抑郁活性，因此没有明显的临床后果。在标准化剂量相同的情况下，女性似乎比男性表现出更高的未代谢甲丙氨酯血浆水平，这是由于较低的蛋白结合率而非更活跃的代谢。在接受联合用药的患者中，吸烟似乎不会诱导甲丙氨酯的去甲基化。通过方差分析和Wilcoxon无分布检验比较的血浆代谢比受性别显著影响，而不受吸烟影响。
