741 
The Pharmacokinetics of Saquinavir in New Tablet Formulation + Ritonavir (1000/100 mg Twice Daily) in HIV-1-infected Pregnant Women
David Burger*1,2, David Burger*1,2, A Eggink1, I Van der Ende3, D Hawkins4, M Vogel5, G Fatkenheuer6, J Molto7, C Richter8, P Koopmans1,2, P Koopmans1,2, M Schutz9, and the SARA study group
1Radboud Univ Med Ctr, Nijmegen, The Netherlands; 2Nijmegen Univ Ctr for Infectious Diseases, The Netherlands; 3Erasmus Med Ctr, Rotterdam, The Netherlands; 4Chelsea and Westminster Hosp, London, UK; 5Univ Hosp, Bonn, Germany; 6Univ Hosp Cologne, Germany; 7Hosp Germans Trial i Pujol, Barcelona, Spain; 8Rijnstate Hosp Arnhem, The Netherlands; and 9Roche Pharma, Basel, Switzerland
Background: HIV-infected pregnant women are recommended to
use a triple-drug HAART regimen to prevent mother-to-child transmission (MCTC),
but there is no consensus as to which third agent should be added to a
combination of 2 nucleoside reverse transcriptase inhibitors (NRTI). Non-NRTI (NNRTI)
are contra-indicated because of teratogenicity
(efavirenz) or an increased risk of hepatotoxicity (nevirapine).
Among the 8 currently available protease inhibitors (PI), 4 agents have FDA
classification B (nelfinavir [NFV], saquinavir [SQV], atazanavir
[ATV], and ritonavir [RTV]), whereas the safety of
the other 4 PI appears to be less certain (FDA classification C). SQV’s new formulation (500-mg tablets) + RTV could be an
attractive option because of proven antiviral efficacy, good tolerability, and
low pill burden, but there are no data available on the pharmacokinetics during
pregnancy.
Methods: In this prospective multicenter
study, 14 HIV-1-infected pregnant women started taking SQV in the new 500-mg
tablet formulation + RTV at the licensed dose of 1000/100 mg twice daily + 2
NRTI. At week 33 (±2 weeks), a 12-hour pharmacokinetic curve was recorded.
Blood was sampled prior to dosing with a standardized breakfast and at t = 1, 2, 3, 4, 6, 8, 10, and 12 hours
post-dosing. Pharmacokinetic parameters were calculated using WinNonlin software version 4.1.
Results: Mean (+ standard deviation [SD]) values for SQV
AUC0-12h, Cmax and Cmin were 19.3 (7.4) mg/L·h,
3.8 (1.5) mg/L, and 1.4 (0.78) mg/L, respectively. For RTV mean values for AUC0-12h,
Cmax and Cmin
were 5.8 (2.5) mg/L·h, 1.1 (0.51) mg/L, and 0.44
(0.22) mg/L, respectively. SQV pharmacokinetic parameters were comparable to
those observed in a previous study using the same formulation in non-pregnant
subjects at the licensed dose of 1000/100 mg twice daily. None of the 14 women
showed a subtherapeutic Cmin
of SQV (defined as <0.10 mg/L. For 2 women a 12-hour pharmacokinetic curve
was also recorded during the second trimester (week 20) or 4 to 6 weeks
post-partum. SQV pharmacokinetic parameters in these patients were not
different from those observed during third trimester.
Conclusions: SQV pharmacokinetics when taken as the new 500-mg
tablet formulation and boosted with RTV at a dose of 1000/100 mg twice daily were
adequate in all 14 women investigated. In contrast to observations with other PI
(ie, NFV, lopinavir/RTV), SQV
pharmacokinetics appear not to be influenced by pregnancy.
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