TUPE278 - Poster Exhibition
Pharmacokinetics, cord blood concentrations, and tolerability of boosted fosamprenavir (FPV) in pregnancy
M. Cespedes1, S. Ford2, G. Pakes2, L. Vargas1, E. De Candia1, J. Aberg1
1New York University School of Medicine, New York, United States, 2GlaxoSmithKline, Research Triangle Park, United States
Background: Plasma concentrations of several protease inhibitors commonly used to prevent vertical HIV transmission are suboptimal during pregnancy. Limited data exist on plasma concentrations of FPV's active metabolite, amprenavir (APV), in maternal plasma throughout pregnancy and in infant cord blood. Safety and outcomes data in pregnancy are also warranted.
Methods: A phase I, open-label, single-center study was conducted to evaluate APV pharmacokinetics (PK) following administration of FPV/RTV 700/100mg twice daily in pregnant HIV-infected women. Steady-state PK was evaluated in the second and/or third trimesters and 4-12 weeks postpartum. Maternal serum and cord blood samples were obtained at the time of delivery. Plasma APV concentrations were measured by LC-MS/MS, and PK were determined using WinNonlin.
Results: PK data were obtained from 10 women (5 African-Americans/5 Hispanics; median age 28.6 years). The regimen most frequently co-administered was tenofovir/emtricitabine. FPV was well tolerated with no hepatic, renal, or adverse events attributed to antiretroviral therapy. At delivery, all had viral loads < 400c/mL with 9 undetectable (< 50c/mL). Median gestational age and birth weight were 37.9 weeks and 2909g. All infants were HIV PCR-negative. No growth abnormalities were observed. Cord blood was obtained from six deliveries; median ratio of cord blood/maternal APV level was 0.27. Individual APV AUC was 22-34% lower, Cmax 9-41% lower and C12 27-28% lower in pregnancy than postpartum.
[Table 1: Amprenavir Concentrations (Median, Range) During Pregnancy]
|Phase||Second Trimester (n=6)||Third Trimester (n=9)||Postpartum (n=9)|
|AUC (μg*h/mL)||26.80 (18.49-40.72)||32.77 (17.05-66.42)||41.73 (28.86-79.66)|
|Cmax (μg/mL)||4.32 (3.07-5.87)||5.75 (3.26-10.98)||6.92 (3.56-9.967)|
|C12h (μg/mL)||1.35 (0.88-1.67)||1.46 (0.66-2.33)||2.24 (1.17-5.32)|
Conclusions: FPV use during pregnancy was well tolerated. Although APV C12 was 27-28% lower in pregnancy, HIV was well suppressed for all subjects at delivery. Maternal and cord blood concentrations were above mean protein binding-adjusted IC50 (0.146µg/mL) for wild-type virus.
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