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 Monolix 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.
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 Monolix 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.
Authors: Angela P H Colbers; David A Hawkins; Andrea Gingelmaier; Kabamba Kabeya; Jürgen K Rockstroh; Christopher Wyen; Katharina Weizsäcker; S Tariq Sadiq; Jelena Ivanovic; Carlo Giaquinto; Graham P Taylor; José Moltó; David M Burger Journal: AIDS Date: 2013-03-13 Impact factor: 4.177
Authors: Patricia M Flynn; Mark Mirochnick; David E Shapiro; Arlene Bardeguez; John Rodman; Brian Robbins; Sharon Huang; Susan A Fiscus; Koen K A Van Rompay; James F Rooney; Brian Kearney; Lynne M Mofenson; D Heather Watts; Patrick Jean-Philippe; Barbara Heckman; Edwin Thorpe; Amanda Cotter; Murli Purswani Journal: Antimicrob Agents Chemother Date: 2011-09-06 Impact factor: 5.191
Authors: Gottfried Hirnschall; Anthony D Harries; Philippa J Easterbrook; Meg C Doherty; Andrew Ball Journal: J Int AIDS Soc Date: 2013-06-30 Impact factor: 5.396
Authors: J B Dumond; J W Collins; M L Cottrell; C R Trezza; Hma Prince; C Sykes; C Torrice; N White; S Malone; R Wang; K B Patterson; N E Sharpless; A Forrest Journal: CPT Pharmacometrics Syst Pharmacol Date: 2016-12-26