Pacifici G M, Cuoci L, Placidi G F
Eur J Drug Metab Pharmacokinet. 1983 Jul-Sep;8(3):209-17. doi: 10.1007/BF03188750.
The pharmacokinetics, distribution, plasma protein binding and the biliary excretion of pinazepam were studied in the rat. The drug was administered (5 mg/kg) by i.p. injection. The chemical analysis of pinazepam and its metabolites was carried out by a gas-chromatographic method. The parent compound was rapidly absorbed, accumulated into the tissues and converted into N-desmethyldiazepam. The highest plasma levels of the parent compound (367 +/- 13 ng/ml) were found 3 min after administration. The volume of distribution and the clearance of the drug were 1315 ml and 7.23 ml/min respectively. The metabolite was detected in the plasma and tissues 3 min after administration. At this sampling time its concentrations were 76 +/- 16 ng/ml in the plasma and 1081 +/- 68 ng/g in the liver. The decay curve of both pinazepam and N-desmethyldiazepam in the plasma, liver, lung, heart, kidney, brain, and gastrochemius muscle were characterized for their Kel, t 1/2, and AUC values. The tissue AUC to plasma AUC ratios indicated a preferential accumulation of pinazepam over its metabolite in the tissues. The plasma protein binding of pinazepam was measured by dialysis at the equilibrium. Rat plasma proteins bound 89.17 +/- 0.20 percent of the drug. The association constant was 2.60 X 10(3) l/mole and the number of sites 0.44 X 10(-6) sites/g. The biliary excretion of pinazepam and N-desmethyldiazepam was poor.
在大鼠体内研究了匹那西泮的药代动力学、分布、血浆蛋白结合及胆汁排泄情况。通过腹腔注射给予该药物（5毫克/千克）。采用气相色谱法对匹那西泮及其代谢产物进行化学分析。母体化合物迅速吸收，蓄积于组织中并转化为N-去甲基地西泮。给药后3分钟测得母体化合物的最高血浆浓度为（367±13纳克/毫升）。药物的分布容积和清除率分别为1315毫升和7.23毫升/分钟。给药后3分钟在血浆和组织中检测到代谢产物。在此取样时间，其在血浆中的浓度为76±16纳克/毫升，在肝脏中的浓度为1081±68纳克/克。对匹那西泮和N-去甲基地西泮在血浆、肝脏、肺、心脏、肾脏、脑及腓肠肌中的衰减曲线进行了Kel、t 1/2和AUC值的表征。组织AUC与血浆AUC之比表明匹那西泮在组织中比其代谢产物更易蓄积。通过平衡透析法测定了匹那西泮的血浆蛋白结合情况。大鼠血浆蛋白结合了89.17±0.20%的药物。结合常数为2.60×10³升/摩尔，结合位点数量为0.44×10⁻⁶位点/克。匹那西泮和N-去甲基地西泮的胆汁排泄较差。
