Atazanavir Pharmacokinetics With and Without Tenofovir During Pregnancy

作者：Mirochnick Mark^*; Best Brookie M; Stek Alice M; Capparelli Edmund V; Hu Chengcheng; Burchett Sandra K; Rossi Steven S; Hawkins Elizabeth; Basar Michael; Smith Elizabeth; Read Jennifer S

来源：JAIDS: Journal of Acquired Immune Deficiency Syndromes , 2011, 56(5): 412-419.

DOI：10.1097/QAI.0b013e31820fd093

• atazanavir
• HIV
• mother to child transmission
• pharmacokinetics
• pregnancy
• tenofovir

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 1026s 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.

• 出版日期2011-4-15