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Modified renal function in pregnancy: impact on emtricitabine pharmacokinetics
Author(s) -
Valade Elodie,
Tréluyer JeanMarc,
Dabis François,
Arrivé Elise,
Pannier Emmanuelle,
Benaboud Sihem,
Fauchet Floris,
Bouazza Naïm,
Foissac Frantz,
Urien Saïk,
Hirt Déborah
Publication year - 2014
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12457
Subject(s) - pregnancy , medicine , pharmacokinetics , renal function , population , obstetrics , gestation , gynecology , genetics , environmental health , biology
Aims 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. Methods 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 M onolix 4.1.3. Results 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%. Conclusions 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.