title: Effect of pregnancy on emtricitabine pharmacokinetics.
abstract: OBJECTIVE
  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 200 mg 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 0.0118 mg/L. The target emtricitabine area under the concentration versus time curve, from time 0 to 24 hours post dose (AUC(0-24) ), was ≥7 mg h/L (≤30% reduction from the typical AUC of 10 mg h/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) mg h/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.
authors: Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles, CA, USA. stek@usc.edu
authors: A M
authors: AM
authors: Stek
authors: B M
authors: BM
authors: Best
authors: W
authors: W
authors: Luo
authors: E
authors: E
authors: Capparelli
authors: S
authors: S
authors: Burchett
authors: C
authors: C
authors: Hu
authors: H
authors: H
authors: Li
authors: J S
authors: JS
authors: Read
authors: A
authors: A
authors: Jennings
authors: E
authors: E
authors: Barr
authors: E
authors: E
authors: Smith
authors: S S
authors: SS
authors: Rossi
authors: M
authors: M
authors: Mirochnick
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism* / Q000821:virology; D006801:Humans; D020128:Inhibitory Concentration 50; D008657:Metabolic Clearance Rate; D049590:Postpartum Period; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy / Q000378:metabolism*; D011263:Pregnancy Trimester, Third; D011446:Prospective Studies; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D003841:Deoxycytidine; D000068679:Emtricitabine