title: Pharmacokinetics of an increased atazanavir dose with and without tenofovir during the third trimester of pregnancy.
abstract: BACKGROUND
  Reduced atazanavir exposure has been demonstrated during pregnancy with standard atazanavir/ritonavir dosing. We studied an increased dose during the third trimester of pregnancy.
  
  
  METHODS
  International Maternal Pediatric Adolescent AIDS Clinical Trials Group 1026s is a prospective, nonblinded, pharmacokinetic study of HIV-infected pregnant women taking antiretrovirals for clinical indications, including 2 cohorts (with or without tenofovir) receiving atazanavir/ritonavir 300/100 mg once daily during the second trimester, 400/100 mg during the third trimester, and 300/100 mg postpartum (PP). Intensive steady-state 24-hour pharmacokinetic profiles were performed. Atazanavir concentrations were measured by high-performance liquid chromatography. Pharmacokinetic targets were the 10th percentile atazanavir area under the concentration versus time curve (AUC) (29.4 μg·hr·mL·) in nonpregnant adults on standard dose and 0.15 μg/mL, minimum trough concentration.
  
  
  RESULTS
  Atazanavir pharmacokinetic data were available for 37 women without tenofovir, 35 with tenofovir; median (range) pharmacokinetic parameters are presented for second trimester, third trimester, and PP and number who met target/total. ATAZANAVIR WITHOUT TENOFOVIR: AUC 30.5 (9.19-93.8), 45.7 (11-88.3), and 48.8 (9.9-112.2) μg·hr·mL, and 8/14, 29/37, and 27/34 met target. C24 h was 0.49 (0.09-4.09), 0.71 (0.14-2.09), and 0.90 (0.05-2.73) μg/mL; 13/14, 36/37, and 29/34 met target. ATAZANAVIR WITH TENOFOVIR: AUC 26.2 (6.8-60.9) (P < 0.05 compared with PP), 37.7 (0.72-88.2) (P < 0.05 compared with PP), and 58.6 (6-149) μg·hr·mL, and 7/17, 23/32, and 27/29 met target. C24 h was 0.44 (0.12-1.06) (P < 0.05 compared with PP), 0.57 (0.02-2.06) (P < 0.05 compared with PP), and 1.26 (0.09-5.43) μg/mL; 7/17, 23/32, and 27/29 met target. Atazanavir/ritonavir was well tolerated with no unanticipated adverse events.
  
  
  CONCLUSIONS
  Atazanavir/ritonavir increased to 400/100 mg provides adequate atazanavir exposure during the third trimester and should be considered during the second trimester.
authors: HIV/AIDS Research Department, Irmandade da Santa Casa de Misericordia de Porto Alegre, RS, Brazil. regis.kr@terra.com.br
authors: Regis
authors: R
authors: Kreitchmann
authors: Brookie M
authors: BM
authors: Best
authors: Jiajia
authors: J
authors: Wang
authors: Alice
authors: A
authors: Stek
authors: Edmund
authors: E
authors: Caparelli
authors: D Heather
authors: DH
authors: Watts
authors: Elizabeth
authors: E
authors: Smith
authors: David E
authors: DE
authors: Shapiro
authors: Steve
authors: S
authors: Rossi
authors: Sandra K
authors: SK
authors: Burchett
authors: Elizabeth
authors: E
authors: Hawkins
authors: Mark
authors: M
authors: Byroads
authors: Tim R
authors: TR
authors: Cressey
authors: Mark
authors: M
authors: Mirochnick
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000069446:Atazanavir Sulfate; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D009842:Oligopeptides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D063065:Organophosphonates / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D049590:Postpartum Period; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000821:virology; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D011446:Prospective Studies; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000068698:Tenofovir; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; D000069446:Atazanavir Sulfate; D000068698:Tenofovir; D000225:Adenine
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