title: Transplacental distribution of chloroquine in sheep.
abstract: Chloroquine is frequently used during pregnancy in malaria-endemic countries, but no data are available about fetal exposure to the drug. Prophylactic use during labour to obtain effective concentrations in the newborn is also documented. In the present study, the placental transfer of chloroquine was investigated in the pregnant, near-term sheep model. Chronic catheterization allowed blood sampling of maternal and fetal blood. Following a single intramuscular injection or intravenous infusion to the ewe, chloroquine was slowly distributed to the fetus. Peak concentrations in the fetus reached up to +/- 280 ng/ml within 2-4 h after administration while maximal concentrations in the mother reached up to 2,850 ng/ml. The terminal half-life of chloroquine in pregnant sheep was very long, amounting to 65.1 +/- 34.9 h (range 27.4-119 h). Tissue binding was high, as reflected by the extensive volume of distribution (V(area): 19.0 +/- 11.0 l/kg). Total clearance was equal to 3.42 +/- 0.60 ml/min/kg. The transfer rate of chloroquine from the mother to the fetus was low in all animals. So, the placenta is quite an effective barrier for the drug.
authors.affiliation: Laboratory of Clinical Pharmacy, University of Leuven, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Augustijns
authors.forename: H W
authors.initials: HW
authors.lastname: Jongsma
authors.forename: N
authors.initials: N
authors.lastname: Verbeke
mesh_terms: D000818:Animals; D002738:Chloroquine / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D005333:Fetus / Q000378:metabolism; D006207:Half-Life; D007273:Injections, Intramuscular; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012756:Sheep
chemical_list: D002738:Chloroquine; C033490:N,N-dideethylchloroquine; C007278:desethylchloroquine