Quinine distribution in pregnant mice with Plasmodium berghei malaria.
Maternal malaria is associated with placental insufficiency that leads to intrauterine growth retardation and reduced birth weight. Malaria may impair the exchange of drugs across the placenta especially the transmission of antimalarial drugs to the foetus. The distribution of quinine and its 3-hydroxymetabolite in blood, tissues and foeto-placental unit was evaluated on day 18 of pregnancy of mice infected or not with Plasmodium berghei. During pregnancy, quinine distribution volume increases gradually with the rise of free quinine concentrations in plasma. Quinine concentrations increase in erythrocytes and most tissues without change in systemic clearance. A maternal-to-foetal gradient of 8:1 limits the exposure of foetus to quinine. During malaria, the systemic clearance of quinine and the 3-hydroxyquinine gradually decrease with the rising parasitaemia. Quinine concentrations increase slightly in most of the tissues. The weight of placentas decreases in a parasitaemia-dependant manner and is strongly related to the low uptake of quinine by placenta. Foetal weights and quinine concentrations in foetus only decrease for the highest parasitaemia. In this experimental model, pregnancy facilitates quinine uptake by erythrocytes and peripheral tissues. Malaria induces a hypotrophy of both placenta and foetus. In placenta, the marked decrease of quinine concentrations may impair the clearance of sequestered parasites.
Lirussi
Frédéric
F
Hopital de Bicetre, Department de Pharmacology, 94275 Le Kremlin Bicetre, France.
Pussard
Eric
E
D000818:Animals; D000962:Antimalarials / Q000097:blood / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus / Q000378:metabolism; D008288:Malaria / Q000097:blood / Q000378:metabolism* / Q000469:parasitology; D051379:Mice; D010920:Placenta / Q000378:metabolism; D010962:Plasmodium berghei / Q000302:isolation & purification*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000097:blood / Q000378:metabolism*; D011802:Quinidine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
D000962:Antimalarials; C013569:3-hydroxyquinidine; D011802:Quinidine