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Br J Clin Pharmacol. 2008 Apr;65 Suppl 1:47-53. doi: 10.1111/j.1365-2125.2008.03135.x.

The effects of cotrimoxazole or tenofovir co-administration on the pharmacokinetics of maraviroc in healthy volunteers.

Author information

1
Pfizer Global R&D, Sandwich, UK.

Abstract

AIMS:

To assess the potential of cotrimoxazole and tenofovir, drugs which are inhibitors and/or substrates of renal transporters, to alter the pharmacokinetic profile of maraviroc.

METHODS:

Two randomized, placebo-controlled, two-way crossover studies were conducted in healthy male and female subjects. In study 1, 16 subjects, aged 18-45 years, received maraviroc (300 mg b.i.d.) with and without cotrimoxazole (960 mg b.i.d.; 160 mg trimethoprim and 800 mg sulfamethoxazole). In study 2, 12 subjects, aged 21-45 years, received maraviroc (300 mg b.i.d.) with and without tenofovir (300 mg q.d.). For study 1, blood was collected predose and on days 1-7. In study 2, blood was collected predose, on day 1 and days 3-7. In both studies, blood was collected at intervals up to 12 h postdose on day 7. Urine was collected on day 7, 0-12 h post morning dose. Blood and urine were analysed for maraviroc using liquid chromatography/tandem mass spectrometry.

RESULTS:

The geometric mean ratios for C(max) and AUC(12) were 119% and 111%, respectively, for maraviroc plus cotrimoxazole and 104% and 103%, respectively, for maraviroc plus tenofovir, compared with maraviroc plus placebo. Renal clearance of maraviroc plus placebo was 8.3 l h(-1) and 8.5 l h(-1) and was 7.8 l h(-1) for maraviroc plus cotrimoxazole and maraviroc plus tenofovir. There were no serious or severe adverse events or any clinically significant changes in laboratory tests, blood pressure, or electrocardiograms.

CONCLUSIONS:

Neither cotrimoxazole nor tenofovir caused a clinically significant effect on the pharmacokinetics of maraviroc. Maraviroc 300 mg b.i.d. was well tolerated when co-administered with either cotrimoxazole or tenofovir.

PMID:
18333865
PMCID:
PMC2311416
DOI:
10.1111/j.1365-2125.2008.03135.x
[Indexed for MEDLINE]
Free PMC Article

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