Document Detail


Pharmacokinetics of an increased atazanavir dose with and without tenofovir during the third trimester of pregnancy.
MedLine Citation:
PMID:  23392467     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Regis Kreitchmann; Brookie M Best; Jiajia Wang; Alice Stek; Edmund Caparelli; D Heather Watts; Elizabeth Smith; David E Shapiro; Steve Rossi; Sandra K Burchett; Elizabeth Hawkins; Mark Byroads; Tim R Cressey; Mark Mirochnick
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Publication Detail:
Type:  Clinical Trial; Journal Article; Multicenter Study; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of acquired immune deficiency syndromes (1999)     Volume:  63     ISSN:  1944-7884     ISO Abbreviation:  J. Acquir. Immune Defic. Syndr.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-11     Completed Date:  2013-06-24     Revised Date:  2014-05-07    
Medline Journal Info:
Nlm Unique ID:  100892005     Medline TA:  J Acquir Immune Defic Syndr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  59-66     Citation Subset:  IM; X    
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00042289
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MeSH Terms
Descriptor/Qualifier:
Adenine / administration & dosage,  analogs & derivatives*,  pharmacokinetics,  therapeutic use
Adolescent
Adult
Anti-HIV Agents / administration & dosage,  pharmacokinetics*,  therapeutic use
Dose-Response Relationship, Drug
Drug Administration Schedule
Drug Therapy, Combination
Female
HIV Infections / drug therapy*,  virology
HIV Protease Inhibitors / administration & dosage,  pharmacokinetics*
HIV-1 / drug effects
Humans
Oligopeptides / administration & dosage,  pharmacokinetics*,  therapeutic use
Organophosphonates / administration & dosage,  pharmacokinetics*,  therapeutic use
Postpartum Period
Pregnancy
Pregnancy Complications, Infectious / drug therapy*,  virology
Pregnancy Trimester, Second
Pregnancy Trimester, Third*
Prospective Studies
Pyridines / administration & dosage,  pharmacokinetics*,  therapeutic use
Reverse Transcriptase Inhibitors / administration & dosage,  pharmacokinetics*,  therapeutic use
Treatment Outcome
Young Adult
Grant Support
ID/Acronym/Agency:
1 U01 AI068616/AI/NIAID NIH HHS; 5 U01 AI41110/AI/NIAID NIH HHS; AI068632/AI/NIAID NIH HHS; N01-DK-9-001/DK/NIDDK NIH HHS; U01 AI041110/AI/NIAID NIH HHS; U01 AI068616/AI/NIAID NIH HHS; U01 AI068632/AI/NIAID NIH HHS; U01 AI068632/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 0/HIV Protease Inhibitors; 0/Oligopeptides; 0/Organophosphonates; 0/Pyridines; 0/Reverse Transcriptase Inhibitors; 107021-12-5/tenofovir; JAC85A2161/Adenine; QZU4H47A3S/atazanavir
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