The effect of ABCB1 polymorphism on the pharmacokinetics of saquinavir alone and in combination with ritonavir

被引：16

作者：

la Porte, C. J. L. ^{[1
]}

Li, Y.

Beique, L.

Foster, B. C.

Chauhan, B.

Garber, G. E.

Cameron, D. W.

van Heeswijk, R. P. G.

机构：

[1] Ottawa Hosp, Ottawa Hlth, Res Inst, Div Infect Dis, Ottawa, ON, Canada

[2] Univ Ottawa, Dept Med, Ottawa, ON K1N 6N5, Canada

[3] Hlth Canada, Off Sci, Therapeut Prod Directorate, Ottawa, ON, Canada

[4] Univ Ottawa, Ctr Res Biopharmaceut, Ottawa, ON K1N 6N5, Canada

来源：

CLINICAL PHARMACOLOGY & THERAPEUTICS | 2007年 / 82卷 / 04期

关键词：

D O I：

10.1038/sj.clpt.6100157

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

This genotype panel study investigated the effect of ABCB1 polymorphism in exon 26 ( C3435T), exon 21 ( G2677T/ A), and exon 12 ( C1236T) on saquinavir pharmacokinetics and on the expression and activity of P-glycoprotein ( P-gp) in peripheral blood monocytic cells ( PBMCs). One hundred and fifty healthy volunteers were genotyped to identify 15 TT3435 and 15 CC3435 individuals. In these individuals, saquinavir pharmacokinetics were assessed after administration of a single oral dose of saquinavir 1,000 mg and saquinavir/ritonavir 1,000/100mg. PBMC P-gp expression and activity were assessed in 15 and 19 subjects. The co-administration of ritonavir on study day 2 caused a significant increase in saquinavir exposure, in both TT3435 and CC3435 individuals. No correlation was observed between the ABCB1 C3435T, G2677T/ A, and C1236T polymorphisms, separately and in haplotypes, with saquinavir pharmacokinetics, administered with or without ritonavir and with PBMC P-gp expression and activity. In conclusion, ABCB1 polymorphism has no pronounced effect on saquinavir exposure.

引用

页码：389 / 395

页数：7

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