Effect of pregnancy on emtricitabine pharmacokinetics

Academic Article


  • Objectives: The aim of the study was to describe emtricitabine pharmacokinetics during pregnancy and postpartum. Methods: The International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT), formerly Pediatric AIDS Clinical Trials Group (PACTG), study P1026s is a prospective pharmacokinetic study of HIV-infected pregnant women taking antiretrovirals for clinical indications, including a cohort taking emtricitabine 200mg once daily. Intensive steady-state 24-hour emtricitabine pharmacokinetic profiles were performed during the third trimester and 6-12 weeks postpartum, and on maternal and umbilical cord blood samples collected at delivery. Emtricitabine was measured by liquid chromatography-mass spectrometry with a quantification limit of 0.0118mg/L. The target emtricitabine area under the concentration versus time curve, from time 0 to 24 hours post dose (AUC 0-24), was ≥7mgh/L (≤30% reduction from the typical AUC of 10mgh/L in nonpregnant historical controls). Third-trimester and postpartum pharmacokinetics were compared within subjects. Results: Twenty-six women had pharmacokinetics assessed during the third trimester (median 35 weeks of gestation) and 22 postpartum (median 8 weeks postpartum). Mean [90% confidence interval (CI)] emtricitabine pharmacokinetic parameters during the third trimester vs. postpartum were, respectively: AUC: 8.0 (7.1-8.9) vs. 9.7 (8.6-10.9) mgh/L (P=0.072); apparent clearance (CL/F): 25.0 (22.6-28.3) vs. 20.6 (18.4-23.2) L/h (P=0.025); 24 hour post dose concentration (C 24): 0.058 (0.037-0.063) vs. 0.085 (0.070-0.010) mg/L (P=0.006). The mean cord:maternal ratio was 1.2 (90% CI 1.0-1.5). The viral load was <400 HIV-1 RNA copies/mL in 24 of 26 women in the third trimester, in 24 of 26 at delivery, and in 15 of 19 postpartum. Within-subject comparisons demonstrated significantly higher CL/F and significantly lower C 24 during pregnancy; however, the C 24 was well above the inhibitory concentration 50%, or drug concentration that suppresses viral replication by half (IC 50) in all subjects. Conclusions: While we found higher emtricitabine CL/F and lower C 24 and AUC during pregnancy compared with postpartum, these changes were not sufficiently large to warrant dose adjustment during pregnancy. Umbilical cord blood concentrations were similar to maternal concentrations. © 2011 British HIV Association.
  • Authors

    Published In

  • HIV Medicine  Journal
  • Digital Object Identifier (doi)

    Author List

  • Stek AM; Best BM; Luo W; Capparelli E; Burchett S; Hu C; Li H; Read JS; Jennings A; Barr E
  • Start Page

  • 226
  • End Page

  • 235
  • Volume

  • 13
  • Issue

  • 4