生理模型同时预报普鲁卡因胺及其代谢物乙酰普鲁卡因胺在大鼠体内处置动力学

用生理模型同时对iv普鲁卡因胺(PA)后,PA及其代谢产物乙酰普鲁卡因胺(NAPA)在大鼠体内处置动力学进行预报。测定了所需的有关PA参数.结果PA在大鼠血液、肝和肾脏清除率分别为47.28,13.56和33.71 ml·kg^-1·min^-1。估算的组织/血液药物浓度比表明,心、肝、肾、肌肉和小畅对PA的亲和力大于血液成分。对大鼠iv PA后,PA及其NAPA在组织中浓度进行预报,并与实验结果比较。结果大多数组织中浓度预报值与观察值基本—致。同时对PA及其NAPA在人血浆中浓度进行了预报。

SIMULTANEOUS PREDICTIONS OF DISPOSITION KINETICS OF PROCAINAMIDE AND ITS METABOLITE N-ACETYLPROCAINAMIDE IN RAT BY A PHYSIOLOGICAL PHARMACOKINETIC MODEL

Disposition kinetics of procainamide (PA) and its metabolite N-acetylprocainamide (NAPA) in rats was simulataneously predicted by a physiological pharmacokinetic model. The parameters, such as clearances in kidney and liver and tissue/blood concentration ratios, which were needed for simulations, were determined. The estimated clearances of PA in rat blood, kidney and liver were 47. 28, 13. 56 and and 33. 71 ml.kg-1.min-1, respectively. Tissue/blood drug concentration ratios were obtained after iv administration according to Gallo's method and demonstrated that heart, liver, kidney, muscle and small intestine have greater affinity for PA than do blood components. The concentrations of PA and NAPA in rat tissues following iv administration of PA.HCl 75 mg/kg were predicted and compared with observed values. The results showed that a good agreement between predictions and observed data was found in most of rat tissues. Concentrations of PA and NAPA in plasma of man, based on scaling-up of kinetics of PA and NAPA from rat to man, was also simulated.