Pharmacokinetics and pharmacodynamics of artesunate and dihydroartemisinin following oral treatment in pregnant women with asymptomatic Plasmodium falciparum infections in Kinshasa DRC

Malaria Journal

Research

Macaya Douoguih¹  David Wesche²  Marie A Onyamboko³  Victor Lokomba³  Joseph Atibu³  Antoinette K Tshefu³  Linda L Wright⁴  Jennifer Hemingway-Foday⁵  Matthew A Koch⁵  Steven R Meshnick⁶  Robert W Ryder⁷  Edmund V Capparelli⁷  Lawrence Fleckenstein⁸  Carl Bose⁹ 

[1] Crucell Holland B.V., Leiden, The Netherlands;David Wesche Consulting LLC, Ann Arbor, MI, USA;Kinshasa School of Public Health, Kinshasa, The Democratic Republic of Congo;National Institute of Child Health and Human Development, NIH, Rockville, MD, USA;RTI International, Research Triangle Park, NC, USA;UNC Gillings School of Global Public Health Department of Epidemiology, 3301 MHRC, 27599-7435, Chapel Hill, NC, USA;University of California, San Diego, CA, USA;University of Iowa, Iowa City, Iowa, USA;University of North Carolina, Chapel Hill, NC, USA;

关键词: Pregnant Woman;    Malaria;    Artesunate;    Artemisinin Derivative;    Intermittent Preventive Treatment;   

DOI  :  10.1186/1475-2875-10-49

 received in 2010-11-29, accepted in 2011-02-28,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundIn many malaria-endemic countries, increasing resistance may soon compromise the efficacy of sulphadoxine-pyrimethamine (SP) for intermittent preventative treatment (IPT) of malaria in pregnancy. Artemisinin-based IPT regimens represent a promising potential alternative to SP. Pharmacokinetic and safety data supporting the use of artemisinin derivatives in pregnancy are urgently needed.MethodsSubjects included pregnant women with asymptomatic falciparum parasitaemia between 22-26 weeks (n = 13) or 32-36 weeks gestation (n = 13), the same women at three months postpartum, and 25 non-pregnant parasitaemic controls. All subjects received 200 mg orally administered AS. Plasma total and free levels of AS and its active metabolite DHA were determined using a validated LC-MS method. Non-compartmental pharmacokinetic analysis was performed using standard methods.ResultsAll pregnant women delivered live babies. The median birth weight was 3025 grams [range 2130, 3620]; 2 of 26 babies had birth weights less than 2500 grams. Rates of parasite clearance by 12 hours post-dose were high and comparable among the groups. Rapid elimination of AS was observed in all three groups. The 90% CI for the pregnancy:postpartum ratio of geometric means for total and free AUC fell within the pre-specified 0.66 - 1.50 therapeutic equivalence interval. However, more pronounced pharmacokinetic differences were observed between the pregnancy and control subjects, with the 90% CI for the pregnancy:control ratio of geometric means for both total 0.68 (90% CI 0.57-0.81) and free AUC 0.78 (90% CI 0.63-0.95) not fully contained within the 0.66 - 1.50 interval. All subjects cleared parasites rapidly, and there was no difference in the percentage of women who were parasitaemic 12 hours after dosing.ConclusionsA single dose of orally administered AS was found to be both effective and without adverse effects in this study of second and third trimester pregnant women in the DRC. Although DHA AUC during pregnancy and postpartum were similar, the AUC for the pregnant group was less than the non-pregnant controls. The findings of this study suggest that additional studies on the pharmacokinetics of AS in pregnant women are needed.Trial RegistrationClinicalTrials.gov: NCT00538382

【 授权许可】

Unknown   
© Onyamboko et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.