title: Efavirenz pharmacokinetics during the third trimester of pregnancy and postpartum.
abstract: BACKGROUND
  The impact of pregnancy on efavirenz (EFV) pharmacokinetics is unknown.
  
  
  METHODS
  International Maternal Pediatric Adolescent AIDS Clinical Trials P1026s is an on-going, prospective, nonblinded study of antiretroviral pharmacokinetics in HIV-infected pregnant women that included a cohort receiving 600 mg EFV once daily as part of combination antiretroviral therapy. Intensive steady-state 24-hour blood sampling was performed during the third trimester and at 6-12 weeks postpartum. Maternal and umbilical cord blood samples were drawn at delivery. Pharmacokinetics targets were the estimated 10th percentile EFV area under the curve (AUC) in nonpregnant historical controls (40.0 mcg·hr(-1)·mL(-1)) and a trough concentration of 1 mcg/mL.
  
  
  RESULTS
  Twenty-five women were enrolled during the third trimester: median (range) age was 29.3 (18.9-42.9) years, weight 69.0 (40-130) kg, and gestational age 32.9 (30.1-38.7) weeks. Median (range) EFV AUC(0-24), C(max), and C(24 hours) were 55.4 mcg·hr(-1)·mL(-1) (13.5-220.3), 5.4 mcg/mL (1.9-12.2), and 1.6 mcg/mL (0.23-8.13), respectively. EFV AUC and C(max) did not differ during pregnancy and postpartum but C(24 hours) was lower during the third trimester (1.6 vs. 2.1 mcg/mL, P = 0.01). During the third trimester, 5 of 25 (20%) women had an EFV AUC below the target and 3 of 25 (12%) had a trough concentration below 1 mcg/mL. EFV cord blood/maternal concentration ratio was 0.49 (0.37-0.74). All women had a HIV-1 RNA viral load less than 400 copies per milliliter at delivery and 19 (76%) had a viral load below 50 copies per milliliter. One child was perinatally HIV infected. Three women were exposed to EFV throughout the first 6 weeks of pregnancy. EFV was well tolerated, and among the 25 infants, no congenital anomalies or newborn complications were reported.
  
  
  CONCLUSIONS
  Changes in EFV pharmacokinetics during pregnancy compared with postpartum are not sufficiently large enough to warrant a dose adjustment during pregnancy.
authors.affiliation: Program for HIV Prevention and Treatment (IRD URI 174), Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand. tim@phpt.org
authors.forename: Tim R
authors.initials: TR
authors.lastname: Cressey
authors.forename: Alice
authors.initials: A
authors.lastname: Stek
authors.forename: Edmund
authors.initials: E
authors.lastname: Capparelli
authors.forename: Chureeratana
authors.initials: C
authors.lastname: Bowonwatanuwong
authors.forename: Sinart
authors.initials: S
authors.lastname: Prommas
authors.forename: Pannee
authors.initials: P
authors.lastname: Sirivatanapa
authors.forename: Prapap
authors.initials: P
authors.lastname: Yuthavisuthi
authors.forename: Chanon
authors.initials: C
authors.lastname: Neungton
authors.forename: Yanling
authors.initials: Y
authors.lastname: Huo
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Smith
authors.forename: Brookie M
authors.initials: BM
authors.lastname: Best
authors.forename: Mark
authors.initials: M
authors.lastname: Mirochnick
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D048588:Benzoxazines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D015331:Cohort Studies; D003521:Cyclopropanes; D005260:Female; D005312:Fetal Blood / Q000276:immunology / Q000821:virology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007231:Infant, Newborn; D049590:Postpartum Period; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D011263:Pregnancy Trimester, Third; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; C098320:efavirenz
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