Gender difference of nimodipine pharmacokinetics in rats

Abstract

Abstract: AIM: To study gender difference in nimodipine (NMD) pharmacokinetics in rats after oral administration NMD and co-administration erythromycin (Ery). METHODS: NMD concentrations in plasma were determined by HPLC after ig administration of 20 mg·kg^-1 NMD and co-administration of 50 mg·kg^-1 Ery, respectively. RESULTS: Marked gender differences for NMD concentrations in rat plasma were found after oral administration of 20 mg·kg^-1 NMD.In groups of NMD alone, the plasma concentrations of NMD in male rats were significantly (P <0.05) lower than those in female rats.AUC value of NMD in male rats was only about one-fourth of that in female rats.In groups for co-administration of Ery, there also exists gender difference;the concentrations of NMD in male rats also were significantly (P <0.05) lower than those in female rats and AUC value of NMD in female rats was about 3.4-folds of that in male rats.In addition, NMD concentration in plasma was significantly increased after co-administration Ery, which AUC values increased 2.0-and 1.6-folds of those in alone NMD, respectively. CONCLUSION: There are marked gender differences in NMD pharmacokinetics of oral administration in rats, and Ery can increase plasma concentrations of NMD.

Key words: nimidipine, gender difference, erythromycin, pharmacokinetics, drug interaction

CLC Number:

R969.1

WANG Xiao-Li, XIE Lin, LIU Xiao-Dong. Gender difference of nimodipine pharmacokinetics in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(5): 532-535.

References

1 Chan LMs, Lowes S, Hirst BH.The ABCs of transporter in intestine and liver:limiting drug absorption and bioavailability [J].Eur J Pharm Sci, 2004;21(1):25-51
2 Zhang L, Liu XD, Xie L, Wang GJ.P-glycoprotein restricted transport of nimodipine across blood-brain barrier [J].Acta Pharmacol Sin, 2003;24(9):903-6
3 Nakajima M, Inoue I, Shimada N, Tokudome S, Yamaoto T, Kuroima Y.Cytochrome P450
4 2C9 catalyzes indomethacin Odemethylation in human liver microsomes[J].2C9 catalyzes indomethacin Odemethylation in human liver microsomes[J].Drug Metab Dispos, 1998;26(3):261-6
5 Los JK, Welsh DA, Herold EG, Bagdon WJ, Zacchei AG. Gender difference in toxicokinetics, liver metabolism, and plasma esterase activity;observation from a chronic(27-weeks) toxicity study of enalapril diltiazem combination in rats[J].Drug Metab Dispos, 1996;24(1):28-33
6 Gorski JJ, Jines DR, Haehner-Daniels BD, Hamman MAO' Marar EM, Jr Hall SD.The contribution of intestinal and hepatic CYP3A to the interaction between midazolam and clarithromycin[J].Clin Pharmacol Ther, 1998;64(4):133-43
7 Liu XD, Xie L, Zhang Y, Li CX.Gender difference in Letrozole pharmacokinetics in rats[J].Acta Pharmacol Sin, 2000;21(8):680-4
8 Liu XD, Xie L, Liang Y, Li L, Lu T.Gender difference in ranolazine pharmacokinetics in rats[J].Eur J Drug Metab Pharmacokinet, 2003;28(2):119-23
9 Wolbold R, Klein K, Burk O, Nussler AK, Neuhaus P, Eichelbaum M, et al.Sex is major determination of CYP 3A expression in liver human[J].Heaptol, 2003;38(4):978-88
10 Kummins Cl, Wu CY, Benet LZ.Sex-related difference in the clearance of cytochrome P450 3A4 substrate may be caused by P-gly coprotein[J].Clin Pharmacol ther, 2002;72(5):474-89
11 Schwartz JB.The influence of sex on pharmacokinetics[J]. Clin Pharmacokinet, 2003;42(2):107-21
12 仝新勇, 黄春玉, 姚静, 谢俊, 周建平.NMD 微乳在小鼠体内的分布及靶向性评价[J].中国药科大学学报, 2002;33(4):293-6
13 Liu XD, Zhang L, Xie L.Effect of P-glycoprotein inhibitors erythromycin and cyclosporin A on brain pharmacokinetics of nimodipine in rats[J].Eur Drug Metabo Pharmacokinet, 2004 in press
14 HC Liu, Jin SM, Wang YL.Gender-related differences in pharmacokinetics of enantiomers of trans-tramadol and its active metabolite, trans-O-demethyltramadol, in rats[J].Acta Pharmacol Sin, 2003;24(12):1265-9

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