Literature DB >> 16470119

Impact of pregnancy on abacavir pharmacokinetics.

Brookie M Best1, Mark Mirochnick, Edmund V Capparelli, Alice Stek, Sandra K Burchett, Diane T Holland, Jennifer S Read, Elizabeth Smith, Chengcheng Hu, Stephen A Spector, James D Connor.   

Abstract

OBJECTIVE: To describe abacavir pharmacokinetics during pregnancy and postpartum; physiological changes during pregnancy are known to affect antiretroviral drug disposition.
DESIGN: The Pediatric AIDS Clinical Trials Group P1026s study is an on-going, prospective, non-blinded pharmacokinetic study of pregnant women receiving one or more antiretroviral drugs for routine clinical care, including a cohort receiving abacavir 300 mg twice daily.
METHODS: Serial plasma samples (predose, 1, 2, 4, and 6 h postdose) obtained antepartum (30-36 weeks of gestation) and again postpartum (6-12 weeks after delivery) were assayed for abacavir concentration by reversed-phase high-performance liquid chromatography.
RESULTS: Antepartum evaluations were available for 25 women [mean age, 28.6 years (SD, 6); mean third-trimester weight 92 kg (SD, 35.4); and race/ethnicity 52% black, 28% Hispanic, 16% white, 4% Asian], with geometric mean abacavir area under the concentration-time curve (AUC) of 5.9 mg.h/l [90% confidence interval (CI), 5.2-6.8] and maximum plasma concentration (Cmax) of 1.9 mg/l (90% CI, 1.6-2.2). Seventeen women completed postpartum sampling, and the ratios of antepartum to postpartum AUC and Cmax were 1.04 (90% CI, 0.91-1.18) and 0.79 (90% CI, 0.65-0.98), respectively.
CONCLUSIONS: Abacavir AUC during pregnancy was similar to that at 6-12 weeks postpartum and to that for non-pregnant historical controls (5.8 mg.h/l). Consequently, pregnancy does not appear to affect overall abacavir exposure significantly or to necessitate dose adjustments.

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Year:  2006        PMID: 16470119     DOI: 10.1097/01.aids.0000210609.52836.d1

Source DB:  PubMed          Journal:  AIDS        ISSN: 0269-9370            Impact factor:   4.177


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