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Atazanavir Pharmacokinetics With and Without Tenofovir during Pregnancy
- Publication Year :
- 2011
-
Abstract
- BACKGROUND Few data are available describing atazanavir exposure during pregnancy, especially when used in combination with tenofovir, whose coadministration with atazanavir results in decreased atazanavir exposure. DESIGN International Maternal Pediatric Adolescent AIDS Clinical Trials 1026 s is an ongoing, prospective, nonblinded study of antiretroviral pharmacokinetics in HIV-infected pregnant women that included 2 cohorts receiving atazanavir/ritonavir 300 mg/100 mg once daily, either with or without tenofovir. METHODS Intensive steady-state 24-hour pharmacokinetic profiles were performed during the third trimester and at 6-12 weeks postpartum. Atazanavir was measured by reverse-phase high-performance liquid chromatography (detection limit 0.047 mcg/mL). Pharmacokinetic targets were the estimated 10th percentile atazanavir area under the concentration versus time curve [(AUC): 29.4 mcg · hr · mL-1] in nonpregnant historical controls (mean AUC = 57 mcg · hr · mL-1) and a trough concentration of 0.15 mcg/mL, the concentration target used in therapeutic drug monitoring programs. RESULTS Median atazanavir AUC was reduced during the third trimester compared with postpartum for subjects not receiving tenofovir (41.9 vs. 57.9 mcg · hr · mL-1, P = 0.02) and for subjects receiving tenofovir (28.8 vs. 39.6 mcg · hr · mL-1, P = 0.04). During the third trimester, AUC was below the target in 33% (6 of 18) of women not receiving tenofovir and 55% (11 of 20) of women receiving tenofovir. Trough concentration was below the target in 6% (1 of 18) of women not receiving tenofovir and 15% (3 of 20) of women receiving tenofovir. The median (range) ratio of cord blood/maternal atazanavir concentration in 29-paired samples was 0.18 (0-0.45). CONCLUSIONS Atazanavir exposure is reduced by pregnancy and by concomitant tenofovir use. A dose increase of atazanavir/ritonavir to 400 mg/100 mg may be necessary in pregnant women to ensure atazanavir exposure equivalent to that seen in nonpregnant adults.
- Subjects :
- medicine.medical_specialty
Anti-HIV Agents
Pyridines
Pregnancy Trimester, Third
Atazanavir Sulfate
Organophosphonates
HIV Infections
Pharmacology
Gastroenterology
Article
Drug Administration Schedule
Pharmacokinetics
Pregnancy
Internal medicine
Medicine
Humans
Pharmacology (medical)
Trough Concentration
Prospective Studies
Pregnancy Complications, Infectious
Tenofovir
Ritonavir
medicine.diagnostic_test
business.industry
Adenine
Postpartum Period
virus diseases
HIV Protease Inhibitors
medicine.disease
Infectious Disease Transmission, Vertical
Atazanavir
Infectious Diseases
Treatment Outcome
Therapeutic drug monitoring
HIV-1
Gestation
Reverse Transcriptase Inhibitors
Drug Therapy, Combination
Female
Drug Monitoring
business
Oligopeptides
Postpartum period
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....ea9ba2cf3145e1f2e5ceb61cd6483bf1