Transfer of chloroquine and desethylchloroquine across the placenta and into milk in Melanesian mothers

I. Law, Kenneth Ilett, L.P. Hackett, M. Page-Sharp, F. Baiwog, S. Gomorrai, I. Mueller, H. Karunajeewa, Timothy Davis

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38 Citations (Scopus)

Abstract

AIMS To investigate the transfer of chloroquine and its major bioactive metabolite desethylchloroquine across the placenta and into breast milk.METHODS In Papua New Guinea, chloroquine (CQ; 25 mg base kg(-1)) is recommended for prophylaxis of malaria during pregnancy, and at the Alexishafen Health Centre women are routinely prescribed CQ at the time of delivery. Fetal-cord and maternal serum samples were collected at delivery (n = 19) and milk samples were collected from day 3 to day 17-21 after delivery (n = 16). CQ and its primary active metabolite desethylchloroquine (DECQ) were quantified by high-performance liquid chromatography. For both CQ and DECQ cord/maternal ratios (C/M) were calculated to characterize placental transfer, and infant exposure via milk was estimated by standard methods.RESULTS The median (interquartile range) C/M was 1.1 (0.9, 1.6) for CQ and 1.2 (0.5, 1.8) for DECQ. The average concentration in milk over the time of sampling was 167 mu g l(-1) (27, 340) for CQ and 54 mu g l(-1) (22, 106) for DECQ. Estimated absolute and relative infant doses were 34 mu g kg(-1) day(-1) (7, 50) and 15 mu g kg(-1) day(-1) (4, 26), and 2.3% (0.5, 3.6) and 1.0% (0.4, 2.0) for CQ and DECQ (as CQ equivalents), respectively.CONCLUSION Infant exposure to CQ and DECQ during pregnancy will be similar to that in the maternal circulation, and dependent on maternal dose and frequency. The median CQ + DECQ relative infant dose of 3.2% (as CQ equivalents) was low, confirming that use of CQ during lactation is compatible with breastfeeding.
Original languageEnglish
Pages (from-to)674-679
JournalBritish Journal of Clinical Pharmacology
Volume65
Issue number5
DOIs
Publication statusPublished - 2008

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