Intersex and interspecies pharmacokinetics of metoprolol after oral and intravenous dose administration in rats and mice

Yeshwant Singh, Ravi Akkireddy, Deepti Sahu, Giridhar Bilagi, Theertha Thykandy, Prajakta Hingole, Deveshkumar Rana, Roopa Naraganti, Sudhir Kumar Tiwari, P. Srivastava
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Abstract

Aim: Intersex and interspecies metoprolol pharmacokinetics following intravenous and oral dose administration in rodents. Materials & methods: Oral and intravenous dose studies were conducted in rats and mice. Significant intersex differences were observed in peak plasma levels of metoprolol after oral dose in both the species. The plasma concentration (Cmax) was approximately sevenfold higher (270.356 ng/ml) in female compared with male rats (40.981 ng/ml) following oral dose administration. The Cmax observed for male (878.822 ± 75.5 ng/ml) was approximately twofold higher than in female mouse (404.016 ± 113.5 ng/ml) after oral dose administration. Conclusion: Sex and species related physioanatomical characteristics alters metoprolol pharmacokinetics. Such differences should be addressed in studies related to metoprolol interactions with concurrently administered drug candidates.
美托洛尔在大鼠和小鼠体内口服和静脉给药后的雌雄和种间药代动力学
目的:研究美托洛尔在啮齿类动物体内静脉和口服给药后的两性和种间药代动力学。材料与方法:对大鼠和小鼠进行口服和静脉给药研究。口服美托洛尔后,两种动物血浆中美托洛尔的峰值水平存在显著的两性差异。口服给药后,雌性大鼠的血药浓度(Cmax)为270.356 ng/ml,约为雄性大鼠(40.981 ng/ml)的7倍。口服给药后,雄性小鼠Cmax(878.822±75.5 ng/ml)比雌性小鼠(404.016±113.5 ng/ml)高约2倍。结论:性别和物种相关的生理解剖特征改变了美托洛尔的药代动力学。这些差异应该在美托洛尔与同时给药的候选药物相互作用的研究中得到解决。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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