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恶性疟原虫感染对孕妇和非孕妇苏丹人体内奎宁及其代谢物药代动力学的影响。

Effects of Plasmodium falciparum infection on the pharmacokinetics of quinine and its metabolites in pregnant and non-pregnant Sudanese women.

机构信息

Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.

出版信息

Eur J Clin Pharmacol. 2010 Dec;66(12):1229-34. doi: 10.1007/s00228-010-0877-3. Epub 2010 Aug 18.

Abstract

PURPOSE

The study aimed to investigate the effects of Plasmodium falciparum infection on the pharmacokinetics of quinine and its metabolites in pregnant and non-pregnant Sudanese women.

METHODS

In a case-control study, nine pregnant and eight non-pregnant Sudanese women infected with P. falciparum were treated with intramuscular artemether. Before being given artemether, they received a single dose of quinine hydrochloride as intravenous infusion. Blood samples were collected frequently and analysed for quinine and its metabolites (phase I). One week later (after clearance of parasitaemia) the quinine part of the protocol was repeated (phase II).

RESULTS

During phase I, the AUCs (mean ± SD) of quinine and its major metaboplite, 3-hydroxyquinine, in pregnant women were 428.2 ± 132.4 and 27.8 ± 14.1 μmol l(-1) h(-1) respectively. In non-pregnant women the AUCs of quinine and 3-hydroxyquinine were 517.8 ± 100.0 and 32.3 ± 15.3 μmol l(-1) h(-1). In pregnant women the mean (90% confidence interval) AUC ratios of phase I to phase II of quinine and 3-hydroxyquinine were 1.6 (0.61, 4.22) and 1.01 (0.18, 5.60). In non-pregnant women, the AUC ratios of phase I to phase II of quinine and 3-hydroxyquinine were 1.93 (1.74, 2.15) and 1.19 (0.95, 1.47).

CONCLUSIONS

Plasmodium falciparum infection significantly increased plasma concentration of quinine in non-pregnant women and showed the same trend in pregnant women.

摘要

目的

本研究旨在探讨恶性疟原虫感染对孕妇和非孕妇中奎宁及其代谢物药代动力学的影响。

方法

采用病例对照研究,9 例感染恶性疟原虫的孕妇和 8 例非孕妇接受肌肉注射青蒿琥酯。在给予青蒿琥酯之前,他们接受了单次静脉注射盐酸奎宁。频繁采集血样并进行分析以检测奎宁及其代谢物(I 相)。一周后(寄生虫血症清除后)重复方案中的奎宁部分(II 相)。

结果

在 I 相中,孕妇奎宁及其主要代谢物 3-羟基奎宁的 AUC(均值±SD)分别为 428.2±132.4 和 27.8±14.1μmol·l-1·h-1。非孕妇奎宁和 3-羟基奎宁的 AUC 分别为 517.8±100.0 和 32.3±15.3μmol·l-1·h-1。孕妇奎宁和 3-羟基奎宁的 I 相与 II 相 AUC 比值的均值(90%置信区间)分别为 1.6(0.61,4.22)和 1.01(0.18,5.60)。在非孕妇中,奎宁和 3-羟基奎宁的 I 相与 II 相 AUC 比值分别为 1.93(1.74,2.15)和 1.19(0.95,1.47)。

结论

恶性疟原虫感染显著增加了非孕妇的奎宁血浆浓度,并在孕妇中表现出相同的趋势。

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