周效磺胺-乙胺嘧啶在肯尼亚西部感染和未感染艾滋病毒的孕妇中的药代动力学

Pharmacokinetics of sulfadoxine-pyrimethamine in HIV-infected and uninfected pregnant women in Western Kenya.

作者信息

Green Michael D, van Eijk Annemieke M, van Ter Kuile Feiko O, Ayisi John G, Parise Monica E, Kager Piet A, Nahlen Bernard L, Steketee Richard, Nettey Henry

机构信息

Division of Parasitic Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.

出版信息

J Infect Dis. 2007 Nov 1;196(9):1403-8. doi: 10.1086/522632. Epub 2007 Oct 2.

DOI:10.1086/522632

PMID:17922406

Abstract

BACKGROUND

Sulfadoxine-pyrimethamine (SP) is among the most commonly used antimalarial drugs during pregnancy, yet the pharmacokinetics of SP are unknown in pregnant women. HIV-infected (HIV(+)) women require more frequent doses of intermittent preventive therapy with SP than do HIV-uninfected (HIV(-)) women. We investigated whether this reflects their impaired immunity or an HIV-associated alteration in the disposition of SP.

METHODS

Seventeen pregnant HIV(-) women and 16 pregnant HIV(+) women received a dose of 1500 mg of sulfadoxine and 75 mg of pyrimethamine. Five HIV(-) and 6 HIV(+) postpartum women returned 2-3 months after delivery for another dose. The pharmacokinetics of sulfadoxine and pyrimethamine were compared between these groups.

RESULTS

HIV status did not affect the area under the curve (AUC(0-->infinity)) or the half-lives of sulfadoxine or pyrimethamine in prepartum or postpartum women, although partum status did have a significant affect on sulfadoxine pharmacokinetics. Among prepartum women, the median half-life for sulfadoxine was significantly shorter than that observed in postpartum women (148 vs 256 h; P<.001), and the median AUC(0-->infinity) was ~40% lower (22,816 vs 40,106 microg/mL/h, P<.001). HIV status and partum status did not show any significant influence on pyrimethamine pharmacokinetics.

CONCLUSION

Pregnancy significantly modifies the disposition of SP, whereas HIV status has little influence on pharmacokinetic parameters in pregnant women.

摘要

背景

周效磺胺-乙胺嘧啶（SP）是孕期最常用的抗疟药物之一，但SP在孕妇中的药代动力学尚不清楚。与未感染HIV（HIV(-)）的女性相比，感染HIV（HIV(+)）的女性需要更频繁地服用SP进行间歇性预防治疗。我们调查了这是否反映了她们受损的免疫力或与HIV相关的SP处置改变。

方法

17名未感染HIV的孕妇和16名感染HIV的孕妇接受了1500毫克周效磺胺和75毫克乙胺嘧啶的剂量。5名未感染HIV和6名感染HIV的产后女性在分娩后2至3个月返回接受另一剂药物。比较了这些组之间周效磺胺和乙胺嘧啶的药代动力学。

结果

HIV状态并未影响产前或产后女性的曲线下面积（AUC(0-->无穷大)）或周效磺胺或乙胺嘧啶的半衰期，尽管产时状态确实对周效磺胺的药代动力学有显著影响。在产前女性中，周效磺胺的中位半衰期明显短于产后女性（148对256小时；P<.001），中位AUC(0-->无穷大)低约40%（22,816对40,106微克/毫升/小时，P<.001）。HIV状态和产时状态对乙胺嘧啶的药代动力学没有任何显著影响。