Читать книгу Drug Transporters - Группа авторов - Страница 96

Pregnancy is accompanied by a number of physiologic changes, including increased cardiac output, as well as hepatic and renal blood flow. There has been much interest into adaptive changes in expression of drug transporters within the mother, placenta, and fetus. Pregnant mice exhibit reduced expression of renal mOct1 and 2, as well as mMate1 mRNA and protein [79, 80]. Within the livers of pregnant mice, there is a downregulation of Oct1 with no change in mMate1 levels compared with virgin mice [79]. These data stand in contrast to a study performed in pregnant women prescribed metformin. Notably, the renal clearance of metformin, as well as the endogenous Mate substrate NMN, was markedly increased during mid‐ and late‐pregnancy compared with early pregnancy or the postpartum period [81]. While a significant increase in glomerular filtration rate contributes to enhanced metformin and NMN elimination from the kidneys, the data also suggest enhanced tubular secretion. The mechanism(s) responsible for divergent regulation of the organic cation transport systems during pregnancy (reduced in mice, increased in humans) are unclear and warrant consideration.