Pharmacokinetics of an increased atazanavir dose with and without tenofovir during the third trimester of pregnancy.
J Acquir Immune Defic Syndr
; 63(1): 59-66, 2013 May 01.
Article
em En
| MEDLINE
| ID: mdl-23392467
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
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Complicações Infecciosas na Gravidez
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Terceiro Trimestre da Gravidez
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Piridinas
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Adenina
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Infecções por HIV
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Inibidores da Protease de HIV
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Inibidores da Transcriptase Reversa
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Fármacos Anti-HIV
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Organofosfonatos
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article