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

共 34 条

[1] Association of the multidrug resistance-1 gene single-nucleotide polymorphisms with the tacrolimus dose requirements in renal transplant recipients [J].

Anglicheau, D ;

Verstuyft, CL ;

Laurent-Puig, P ;

Becquemont, L ;

Schlageter, MH ;

Cassinat, B ;

Beaune, P ;

Legendre, C ;

Thervet, E .

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2003, 14 (07) :1889-1896

[2] Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects [J].

Cascorbi, I ;

Gerloff, T ;

Johne, A ;

Meisel, C ;

Hoffmeyer, S ;

Schwab, M ;

Schaeffeler, E ;

Eichelbaum, M ;

Brinkmann, U ;

Roots, I .

CLINICAL PHARMACOLOGY & THERAPEUTICS, 2001, 69 (03) :169-174

[3] The effects of protease inhibitors and nonnucleoside reverse transcriptase inhibitors on P-glycoprotein expression in peripheral blood mononuclear cells in vitro [J].

Chandler, B ;

Almond, L ;

Ford, J ;

Owen, A ;

Hoggard, P ;

Khoo, S ;

Back, D .

JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 2003, 33 (05) :551-556

[4] Genetic polymorphisms in MDR1 and CYP3A4 genes in Asians and the influence of MDR1 haplotypes on cyclosporin disposition in heart transplant recipients [J].

Chowbay, B ;

Cumaraswamy, S ;

Cheung, YB ;

Zhou, QY ;

Lee, EJD .

PHARMACOGENETICS, 2003, 13 (02) :89-95

[5] MDR1 gene polymorphisms and disposition of the P-glycoprotein substrate fexofenadine [J].

Drescher, S ;

Schaeffeler, E ;

Hitzl, M ;

Hofmann, U ;

Schwab, M ;

Brinkmann, U ;

Eichelbaum, M ;

Fromm, MF .

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2002, 53 (05) :526-534

[6] Response to antiretroviral treatment in HIV-1-infected individuals with allelic variants of the multidrug resistance transporter 1: a pharmacogenetics study [J].

Fellay, J ;

Marzolini, C ;

Meaden, ER ;

Back, DJ ;

Buclin, T ;

Chave, JP ;

Decosterd, LA ;

Furrer, H ;

Opravil, M ;

Pantaleo, G ;

Retelska, D ;

Ruiz, L ;

Schinkel, AH ;

Vernazza, P ;

Eap, CB ;

Telenti, A .

LANCET, 2002, 359 (9300) :30-36

[7] Association of the CYP3A5 A6986G (CYP3A5*3) polymorphism with saquinavir pharmacokinetics [J].

Fröhlich, M ;

Hoffmann, MM ;

Burhenne, J ;

Mikus, G ;

Weiss, J ;

Haefeli, WE .

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2004, 58 (04) :443-444

[8] Functional polymorphisms of the human multidrug-resistance gene:: Multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo [J].

Hoffmeyer, S ;

Burk, O ;

von Richter, O ;

Arnold, HP ;

Brockmöller, J ;

Johne, A ;

Cascorbi, I ;

Gerloff, T ;

Roots, I ;

Eichelbaum, M ;

Brinkmann, U .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (07) :3473-3478

[9] Multidrug resistance protein 2 (MRP2) transports HIV protease inhibitors, and transport can be enhanced by other drugs [J].

Huisman, MT ;

Smit, JW ;

Crommentuyn, KML ;

Zelcer, N ;

Wiltshire, HR ;

Beijnen, JH ;

Schinkel, AH .

AIDS, 2002, 16 (17) :2295-2301

[10] Modulation of steady-state kinetics of digoxin by haplotypes of the P-glycoprotein MDR1 gene [J].

Johne, A ;

Köpke, K ;

Gerloff, T ;

Mai, I ;

Rietbrock, S ;

Meisel, C ;

Hoffmeyer, S ;

Kerb, R ;

Fromm, MF ;

Brinkmann, U ;

Eichelbaum, M ;

Brockmöller, J ;

Cascorbi, I ;

Roots, I .

CLINICAL PHARMACOLOGY & THERAPEUTICS, 2002, 72 (05) :584-594

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