健康志愿者中匹那西泮的药代动力学

Pharmacokinetics of pinazepam in healthy volunteers.

作者信息

Pacifici G M, Placidi G F, Fornaro P, Gomeni R

出版信息

Int J Clin Pharmacol Res. 1983;3(5):331-7.

Abstract

The kinetics of pinazepam were studied in six healthy male volunteers aged between 26 and 31 years. The drug was administered in a single oral dose (10 mg). The concentrations of the parent compound and metabolites were measured in the plasma and urine by gas-chromatographic analysis. Plasma levels of pinazepam were fitted to a two-compartment open model with first order absorption rate using a three-exponential equation. Absorption rate constant and peak plasma levels of pinazepam were 1.36 +/- 0.15 h-1 and 36.8 +/- 5.1 ng/ml respectively. Plasma decay of the drug consisted of an initial rapid elimination phase (alpha = 0.46 +/- 0.06 h-1) followed by a slow one (beta = 0.046 +/- 0.004 h-1). N-desmethyldiazepam was the only metabolite detected in the plasma. Its plasma concentrations were higher than those of the parent compound shortly after administration. Urine was collected for 72 h after dosing. Those specimens contained unconjugate pinazepam and N-desmethyldiazepam and glucuronated oxazepam and 3-OH-pinazepam. Only 0.016% of the pinazepam administered was recovered as unchanged compound in the urine.

摘要

在6名年龄在26至31岁之间的健康男性志愿者身上研究了匹那西泮的动力学。以单次口服剂量（10毫克）给药该药物。通过气相色谱分析测定血浆和尿液中母体化合物和代谢物的浓度。使用三指数方程将匹那西泮的血浆水平拟合为具有一级吸收速率的二室开放模型。匹那西泮的吸收速率常数和血浆峰值水平分别为1.36±0.15 h⁻¹和36.8±5.1 ng/ml。药物的血浆消除包括一个初始快速消除阶段（α = 0.46±0.06 h⁻¹），随后是一个缓慢阶段（β = 0.046±0.004 h⁻¹）。N-去甲基地西泮是血浆中检测到的唯一代谢物。给药后不久，其血浆浓度高于母体化合物的浓度。给药后收集尿液72小时。这些样本含有未结合的匹那西泮和N-去甲基地西泮以及葡萄糖醛酸化的奥沙西泮和3-羟基匹那西泮。给药的匹那西泮中只有0.016%以未改变的化合物形式在尿液中回收。