Transfer of chloroquine and desethylchloroquine across the placenta and into milk in Melanesian mothers.
BACKGROUND
The literature on placental and milk transfer of chloroquine and its major bioactive metabolite desethylchloroquine is sparse and incomplete.


CONCLUSIONS
We have provided data on the transplacental transfer of chloroquine and desethylchloroquine in Melanesian women (n = 19), measured transfer of these drugs into breast milk (n = 16) and estimated absolute and relative infant doses for the breastfed infant. The data for desethylchloroquine are novel. In all three areas we have significantly increased both quantity and quality of the available database.


OBJECTIVE
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 microg l(-1) (27, 340) for CQ and 54 microg l(-1) (22, 106) for DECQ. Estimated absolute and relative infant doses were 34 microg kg(-1) day(-1) (7, 50) and 15 microg 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.


CONCLUSIONS
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.
Law
Irwin
I
School of Medicine and Pharmacology, University of Western Australia, Crawley, Australia.
Ilett
Kenneth F
KF
Hackett
L Peter
LP
Page-Sharp
Madhu
M
Baiwog
Francesca
F
Gomorrai
Servina
S
Mueller
Ivo
I
Karunajeewa
Harin A
HA
Davis
Timothy M E
TM
D000328:Adult; D000962:Antimalarials / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001942:Breast Feeding; D002738:Chloroquine / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D008542:Melanesia; D008895:Milk, Human / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000188:drug therapy*
D000962:Antimalarials; D002738:Chloroquine; C007278:desethylchloroquine