title: Suboptimal nevirapine steady-state pharmacokinetics during intrapartum compared with postpartum in HIV-1-seropositive Ugandan women.
abstract: BACKGROUND
  Conflicting data exist regarding the effect of pregnancy on steady-state nevirapine pharmacokinetics (PK), although steady-state nevirapine concentrations during pregnancy have never been characterized in sub-Saharan Africa.
  
  
  METHODS
  This was a longitudinal intensive PK study in Ugandan pregnant women receiving nevirapine-based antiretroviral therapy. Participants underwent intensive 12-hour PK sampling during the second trimester (T2; n = 4), third trimester (T3; n = 15) and 6 weeks postpartum (PP; n = 15). HIV-1 RNA was performed within 2 weeks of each visit. Nevirapine C12 above 3000 ng/mL was classified as optimal based on the suggested value for therapeutic drug monitoring.
  
  
  RESULTS
  The pharmacokinetics of nevirapine were influenced by pregnancy, demonstrated by a 20% reduction in the maximum concentration, minimum concentration (C12), and area under the curve between T3 and PP visits (P = 0.001, P = 0.011 and P = 0.005, respectively). Ten subjects (66.7%) had C12 values <3000 ng/mL during T3. Of these participants, 7 partcipant's C12 concentrations increased to >3000 ng/mL during the PP visit. HIV-1 RNA were <1000 copies per milliliter at T3 and <400 copies per milliliter at PP in all patients.
  
  
  CONCLUSIONS
  Nevirapine exposure was reduced in Ugandan women during their third trimester compared with the same women PP, however, HIV RNA remained <1000 copies per milliliter. The long-term impact of intermittent suboptimal nevirapine concentrations during pregnancy is unknown.
authors.affiliation: Research Department, Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda. mlamorde@idi.co.ug
authors.forename: Mohammed
authors.initials: M
authors.lastname: Lamorde
authors.forename: Pauline
authors.initials: P
authors.lastname: Byakika-Kibwika
authors.forename: Violet
authors.initials: V
authors.lastname: Okaba-Kayom
authors.forename: John P
authors.initials: JP
authors.lastname: Flaherty
authors.forename: Marta
authors.initials: M
authors.lastname: Boffito
authors.forename: Rhoda
authors.initials: R
authors.lastname: Namakula
authors.forename: Mairin
authors.initials: M
authors.lastname: Ryan
authors.forename: Clemensia
authors.initials: C
authors.lastname: Nakabiito
authors.forename: David J
authors.initials: DJ
authors.lastname: Back
authors.forename: Saye
authors.initials: S
authors.lastname: Khoo
authors.forename: Concepta
authors.initials: C
authors.lastname: Merry
authors.forename: Kimberly K
authors.initials: KK
authors.lastname: Scarsi
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008137:Longitudinal Studies; D019829:Nevirapine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D010949:Plasma / Q000737:chemistry / Q000821:virology; D049590:Postpartum Period; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D014454:Uganda; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D019829:Nevirapine