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首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >Pharmacodynamic modeling of pantoprazole's irreversible effect on gastric acid secretion in humans and rats.
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Pharmacodynamic modeling of pantoprazole's irreversible effect on gastric acid secretion in humans and rats.

机译：top托拉唑对人和大鼠胃酸分泌的不可逆作用的药效学模型。

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摘要

The relationship between the pharmacokinetics of pantoprazole, an irreversible proton pump inhibitor, and its effect on gastric acid secretion was evaluated in humans and rats. Pantoprazole pharmacokinetics were studied in 6 rats (5 mg/kg, i.v.) and 22 healthy volunteers (10 to 80 mg, i.v. and oral). Gastric acid secretion under maximum pentagastrin stimulation was measured after i.v. administration of placebo or pantoprazole in 31 rats (0.12 to 1.15 mg/kg) for 4 hours and in 31 subjects (20 to 120 mg) for 24 hours. Pantoprazole has short half-lives of 0.5 hours in rats and 0.8 hours in humans. After administration of the highest dose, acid secretion was fully inhibited within 1 hour and for the whole observation period in both species. An irreversible pharmacodynamic response model was successfully developed and validated. The apparent reaction rate constants of pantoprazole with the proton pumps were 0.691 L/mg/h in rats and 0.751 L/mg/h in humans, and the apparent recovery rates of the pumps were 0.053 h-1 and 0.031 h-1, respectively. The maximum inhibition and the overall effect of pantoprazole are related to exposure, and the onset is related to initial pantoprazole concentrations. It was concluded that this irreversible response model accurately describes the effect of i.v. and oral pantoprazole on gastric secretion and may be used to predict effects under other dosage regimens.
机译：评价了人类和大鼠中不可逆的质子泵抑制剂pan托拉唑的药代动力学与其对胃酸分泌的影响之间的关系。在6只大鼠（5 mg / kg，静脉内）和22位健康志愿者（10至80 mg，静脉内和口服）中研究了top托拉唑的药代动力学。静脉注射后测量最大五肽胃泌素刺激下的胃酸分泌。在31只大鼠（0.12至1.15 mg / kg）中给予安慰剂或pan托拉唑4小时，在31位受试者（20至120 mg）中给予24小时。 top托拉唑的半衰期短，在大鼠中为0.5小时，在人中为0.8小时。给予最高剂量后，两个物种在1小时内和整个观察期内都完全抑制了酸分泌。不可逆的药效学反应模型已成功开发和验证。 pan托拉唑与质子泵的表观反应速率常数在大鼠中为0.691 L / mg / h，在人中为0.751 L / mg / h，在人体中表观回收率分别为0.053 h-1和0.031 h-1。 。 top托拉唑的最大抑制作用和总体作用与暴露有关，而发作与pan托拉唑的初始浓度有关。结论是，这种不可逆的反应模型准确地描述了i.v.和口服pan托拉唑对胃分泌的影响，可用于预测其他剂量方案的作用。

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