Modified renal function in pregnancy: impact on emtricitabine pharmacokinetics

The aims were to describe emtricitabine (FTC) pharmacokinetics in a large population of pregnant women during the different trimesters of pregnancy, and to explain FTC pharmacokinetic variability during pregnancy.

FTC plasma concentrations were measured in 103 non-pregnant and 83 pregnant women, including women in the different trimesters of pregnancy and on the day of delivery. A total of 457 plasma concentrations were available for analysis. A population pharmacokinetic model was developed with Monolix 4.1.3.

FTC pharmacokinetics was best described by a two compartment model. The effect of creatinine clearance on apparent elimination clearance (CL/F) was significant. CL/F in pregnant women was significantly higher compared with non-pregnant women (geometric mean 24.1 vs 20.5 l h(-1) , P < 0.001), reflecting a modified renal function. FTC daily exposures (AUC) during pregnancy were lower than AUC in non-pregnant women, regardless of the trimester of pregnancy. FTC AUC geometric means were 8.38 mg l(-1 ) h in the second trimester of pregnancy, 8.16 mg l(-1 ) h in the third trimester of pregnancy, 8.30 mg l(-1 ) h on the day of delivery and 9.77 mg l(-1 ) h in non-pregnant women. FTC concentrations 24 h after administration were lower in pregnant women compared with non-pregnant women (0.054 vs. 0.079 mg l(-1) , P < 0.001) but still above the inhibitory concentration 50%.

FTC CL/F was increased by 18% during pregnancy, reflecting a modified renal function with 50% increase in estimated glomerular filtration rate. However, the impact of this modified renal function on FTC pharmacokinetics was not sufficiently large to consider dose adjustments during pregnancy.