Lirussi Frédéric, Pussard Eric
Hopital de Bicetre, Department de Pharmacology, 94275 Le Kremlin Bicetre, France.
Eur J Pharm Sci. 2006 Jul;28(4):284-90. doi: 10.1016/j.ejps.2006.03.004. Epub 2006 Mar 22.
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.
孕产妇疟疾与胎盘功能不全有关，可导致胎儿宫内生长受限和出生体重降低。疟疾可能会损害药物通过胎盘的交换，尤其是抗疟药物向胎儿的传递。在感染或未感染伯氏疟原虫的小鼠怀孕第18天时，评估了奎宁及其3-羟基代谢产物在血液、组织和胎盘-胎儿单位中的分布。在怀孕期间，奎宁的分布容积随着血浆中游离奎宁浓度的升高而逐渐增加。红细胞和大多数组织中的奎宁浓度升高，而全身清除率不变。母体与胎儿的浓度梯度为8:1，限制了胎儿对奎宁的暴露。在疟疾期间，随着寄生虫血症的升高，奎宁和3-羟基奎宁的全身清除率逐渐降低。大多数组织中的奎宁浓度略有升高。胎盘重量以寄生虫血症依赖的方式降低，并且与胎盘对奎宁的低摄取密切相关。仅在寄生虫血症最高时，胎儿体重和胎儿体内的奎宁浓度才会降低。在这个实验模型中，怀孕促进了红细胞和外周组织对奎宁的摄取。疟疾会导致胎盘和胎儿萎缩。在胎盘中，奎宁浓度的显著降低可能会损害被隔离寄生虫的清除。
