Artemis Pharmaceutical Research, Jacksonville, Florida.
Birth Defects Res. 2017 Aug 15;109(14):1075-1126. doi: 10.1002/bdr2.1035. Epub 2017 Jun 24.
The World Health Organization currently recommends quinine+clindamycin for use against malaria in the first trimester. This may soon change to recommending artemisinin-based combination therapies (standard duration of dosing = 3 days). The non-artemisinin partner drugs include amodiaquine, lumefantrine, mefloquine, piperaquine, sulfadoxine+pyrimethamine, and pyronaridine. For quinine, clindamycin, and mefloquine and the combinations of sulfadoxine+pyrimethamine and artemether+lumefantrine, there are reports (including studies without internal comparison groups) that combined describe 304 to >1100 exposures of women in the first trimester for each drug with no conclusive evidence of adverse effects on pregnancy at therapeutic doses. This is despite the fact that all of these drugs or drug combinations caused embryo deaths and/or malformations in at least one animal species and all except lumefantrine had at least one exposure ratio <1. It now seems that these animal studies overestimated the risk of developmental toxicity in women with malaria. Three other non-artemisinins (amodiaquine, piperaquine, and pyronaridine) have few or no reported exposures in women in the first trimester and have exposure ratios ≤2 based on studies in pregnant rats and rabbits with dosing throughout organogenesis. However, none of these drugs caused embryo deaths or malformations in pregnant rats and rabbits with the exception of pyronaridine, which caused embryo deaths only at a dose that was excessively toxic to the mothers. Thus, for amodiaquine, piperaquine, and pyronaridine, the testing in animals did not reveal findings of concern and the exposure ratios were in the range of the other non-artemisinin antimalarials described above. Birth Defects Research 109:1075-1126, 2017. © 2017 The Authors. Birth Defects Research Published by Wiley Periodicals, Inc.
世界卫生组织目前建议在妊娠早期使用奎宁+克林霉素治疗疟疾。这种情况可能很快就会改变，改为推荐使用青蒿素为基础的联合疗法（标准剂量疗程= 3 天）。非青蒿素类的联合用药包括阿莫地喹、青蒿琥酯、甲氟喹、哌喹、磺胺多辛+乙胺嘧啶和咯萘啶。对于奎宁、克林霉素和甲氟喹以及磺胺多辛+乙胺嘧啶和青蒿琥酯+蒿甲醚的联合用药，有报道（包括没有内部对照组的研究）称，在治疗剂量下，每种药物在妊娠早期都有 304 至> 1100 次的女性暴露，没有确凿的证据表明这些药物对妊娠有不良影响。尽管所有这些药物或药物组合都导致了至少一种动物物种的胚胎死亡和/或畸形，而且除了青蒿琥酯之外，所有药物的暴露比值都<1。现在看来，这些动物研究高估了患有疟疾的女性发生发育毒性的风险。另外三种非青蒿素类药物（阿莫地喹、哌喹和咯萘啶）在妊娠早期的女性中报告的暴露次数很少或没有，并且基于对在器官发生期接受治疗的妊娠大鼠和家兔的研究，暴露比值≤2。然而，除了咯萘啶之外，这些药物在妊娠大鼠和家兔中都没有引起胚胎死亡或畸形，而咯萘啶仅在对母亲毒性过高的剂量下才引起胚胎死亡。因此，对于阿莫地喹、哌喹和咯萘啶，动物试验未发现令人担忧的发现，并且暴露比值处于上述其他非青蒿素类抗疟药的范围内。出生缺陷研究 109:1075-1126, 2017。© 2017 作者。出生缺陷研究由 Wiley 期刊出版公司出版。
