Therapeutic drug monitoring of atazanavir/ritonavir in pregnancy.
OBJECTIVE
Pregnant women experience physiological changes during pregnancy that can have a significant impact on antiretroviral pharmacokinetics. Ensuring optimal plasma concentrations of antiretrovirals is essential for maternal health and to minimize the risk of vertical transmission. Here we describe atazanavir/ritonavir (ATV/r) plasma concentrations in a cohort of pregnant women undergoing routine therapeutic drug monitoring (TDM).


METHODS
Pregnant HIV-positive women received ATV/r as part of their routine pre-natal care. Demographic and clinical data were collected. ATV plasma concentrations ([ATV]) were determined in the first (T1), second (T2) and third (T3) trimesters and at postpartum (PP) using liquid chromatography-tandem mass spectrometry (LC-MS/MS).


RESULTS
From January 2007, 44 women (37 black African) were enrolled in the study. All received ATV/r at a dose of 300/100 mg once a day. Twenty-four had received antiretroviral therapy (ART) prior to pregnancy, and 20 initiated ATV/r in pregnancy. At the time nearest to delivery, 36 patients had undetectable plasma viral loads. [ATV] values were determined in 11 (T1), 25 (T2), 34 (T3) and 28 (PP) patients. [ATV] at 24 hours post-dose (C24) values significantly lower at T2/T3 relative to PP.


CONCLUSIONS
This study was carried out in one of the larger cohorts of women undergoing TDM for ATV in pregnancy. Lower [ATV] values were seen in T2/T3 compared with T1/PP. However, [ATV] were not associated with a lack of virologic suppression at delivery. Nonetheless, careful monitoring of women in pregnancy is required, and dose adjustment of ATV to 400 mg may be an option.
Department of Molecular & Clinical Pharmacology, University of Liverpool, Liverpool, UK.
L J
LJ
Else
V
V
Jackson
M
M
Brennan
D J
DJ
Back
S H
SH
Khoo
S
S
Coulter-Smith
J S
JS
Lambert
D000328:Adult; D000704:Analysis of Variance; D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000069446:Atazanavir Sulfate; D016903:Drug Monitoring; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D009842:Oligopeptides / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000097:blood* / Q000188:drug therapy; D011725:Pyridines / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019438:Ritonavir / Q000493:pharmacokinetics* / Q000627:therapeutic use; D055815:Young Adult
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; D019438:Ritonavir
atazanavir; pharmacokinetics; pregnancy; therapeutic drug monitoring