Gender-Related Differences in the Expression of Organic Cation Transporter 2 and its Role in Urinary Excretion of Metformin in Rats

doi:10.1007/s13318-015-0278-1

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	Gender-Related Differences in the Expression of Organic Cation Transporter 2 and its Role in Urinary Excretion of Metformin in Rats
	Ma, YR; Qin, HY; Jin, YW; Huang, J; Han, M; Wang, XD; Zhang, GQ; Zhou, Y; Rao, Z; Wu, XA
刊名	EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS
	2016-10
卷号	41 期号:5 页码:559-565
ISSN号	0378-7966
DOI	10.1007/s13318-015-0278-1
文献子类	Article
英文摘要	Organic cation transporter 2 (rOCT2) and multidrug and toxin extrusion protein 1 (rMATE1) are mainly expressed in rat renal proximal tubules and mediate urinary excretion of cationic drugs, such as metformin. Accumulated evidence indicated that renal rOCT2 expression in male rats is much higher than that of female rats. However, it is unclear whether the gender-related differences in rOCT2 expression between male and female rats can affect the urinary excretion of metformin. The aim of this study was to investigate the effect of gender on the pharmacokinetics of metformin and to clarify the effect of gender-related differences on renal rOCT2 expression and its role in urinary excretion of metformin. Renal rOCT2 levels, but not rOCT1 and rMATE1, were significantly lowered in female rats when compared to that of male rats (P < 0.01), while the pharmacokinetic parameters, i.e., AUC(0 -> t), t (1/2), CL/F, and cumulative urinary excretion of metformin, did not show any significant differences between female and male rats following oral administration of metformin at l00 mg/kg (P > 0.05). However, when metformin was orally administered at the dose of 500 mg/kg, the cumulative urinary excretion and renal tissue-to-plasma concentration ratio of metformin in female rats (26,689 +/- A 1266 mu g and 2.96 +/- A 0.47 mL/g, respectively) were markedly lowered compared to that of male rats (32,949 +/- A 1384 mu g and 4.20 +/- A 0.31 mL/g, respectively), and the plasma concentration of metformin in female rats (55.9 +/- A 4.5 mu g/mL) was significantly increased compared to that of male rats (43.5 +/- A 3.1 mu g/mL) at 2 h after oral administration. These results indicated that effect of gender-related differences on renal rOCT2 expression indeed contributes to the decreased urinary excretion of metformin in female rats when metformin was administered at relatively high doses.
学科主题	Pharmacology & Pharmacy
出版地	PARIS
语种	英语
WOS记录号	WOS:000382883400008
内容类型	期刊论文
源URL	[http://ir.lzu.edu.cn/handle/262010/178671]
专题	第一临床医学院_期刊论文
通讯作者	Wu, XA (reprint author), Lanzhou Univ, Hosp 1, Dept Pharm, 1 Donggangxi Rd, Lanzhou 730000, Gansu, Peoples R China.
推荐引用方式 GB/T 7714	Ma, YR,Qin, HY,Jin, YW,et al. Gender-Related Differences in the Expression of Organic Cation Transporter 2 and its Role in Urinary Excretion of Metformin in Rats[J]. EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS,2016,41(5):559-565.
APA	Ma, YR.,Qin, HY.,Jin, YW.,Huang, J.,Han, M.,...&Wu, XA .(2016).Gender-Related Differences in the Expression of Organic Cation Transporter 2 and its Role in Urinary Excretion of Metformin in Rats.EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS,41(5),559-565.
MLA	Ma, YR,et al."Gender-Related Differences in the Expression of Organic Cation Transporter 2 and its Role in Urinary Excretion of Metformin in Rats".EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS 41.5(2016):559-565.