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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Pharmacokinetics of metformin in the rat: assessment of the effect of hyperlipidemia and evidence for its metabolism to guanylurea
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Pharmacokinetics of metformin in the rat: assessment of the effect of hyperlipidemia and evidence for its metabolism to guanylurea

机译：大鼠二甲双胍的药代动力学：对高脂血症和证据对瓜瓜氏菌的影响的评估

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摘要

Metformin pharmacokinetics are highly dependent upon organic cationic transporters. There is evidence of a change in its renal clearance in hyperlipidemic obese patients, and no information on its metabolic fate. To study some of these aspects, the influence of poloxamer 407 (P407)-induced hyperlipidemia on metformin pharmacokinetics was assessed. Control and P407-treated adult male rats were administered 30 mg/kg metformin intravenously (i.v.). The pharmacokinetic assessments were performed at 2 time points, 36 and 108 h, following the intraperitoneal dose of P407 (1 g/kg). mRNA and protein expressions of cationic drug transporters were also measured. There was no evidence of a change in metformin pharmacokinetics after i.v. doses as a consequence of short-term hyperlipidemia, and a change in transportermRNAbut not protein expression was observed in the P407treated rats 108 h after P407 injection. Urinary recovery of unchanged drug was high (>90%) but incomplete. Presumed metabolite peaks were detected in chromatograms of hepatocytes and microsomal protein spiked with metformin. Comparative chromatographic elution times and mass spectra suggested that one of the predominant metabolites was guanylurea. Hyperlipidemia by itself did not affect the pharmacokinetics of metformin. Guanylurea is a putative metabolite of metformin in rats.
机译：二甲双胍药代动力学高度依赖于有机阳离子转运蛋白。有证据表明血糖肥胖患者的肾脏清除变化，没有关于其代谢命运的信息。为研究其中一些方面，评估了泊洛沙姆407（P407） - 诱导的高氧血症对二甲双胍药代动力学的影响。对照和P407处理的成年大鼠静脉内（I.V.）施用30mg / kg二甲双胍。在P407（1g / kg）的腹膜内剂量之后，在2个时间点，36和108小时进行药代动力学评估。还测量阳离子药物转运蛋白的mRNA和蛋白质表达。在i.v之后没有证据表明二甲双胍药代动力学。作为短期高脂血症的后果，在P407注射后在P407过度的大鼠108小时内观察到Transportermrnabut而不是蛋白质表达的变化。未改变药物的尿恢复高（> 90％）但不完整。在肝细胞形式的色谱图中检测到推出的代谢物峰和用二甲双胍掺入微粒体蛋白。对比色谱洗脱时间和质谱表明，主要代谢物之一是胍脲。 HyperiPidemia本身并不影响二甲双胍的药代动力学。 Guanylea是大鼠二甲双胍的推定代谢物。

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