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Pharmacokinetic analysis to assess forgiveness of boosted saquinavir regimens for missed or late dosing.

Dickinson L, Boffito M, Khoo SH, Schutz M, Aarons LJ, Pozniak AL, Back DJ

Department of Pharmacology, University of Liverpool, Liverpool, UK. laurad@liv.ac.uk

OBJECTIVES: One potential concern of once-daily protease inhibitor administration is low trough concentrations and ultimately the 'forgiveness' or robustness in comparison with the originally licensed twice-daily dose. To give an estimation of 'forgiveness', we determined the length of time plasma drug concentrations were below target in HIV-infected patients receiving saquinavir/ritonavir regimens. METHODS: Seventy-seven pharmacokinetic profiles (saquinavir/ritonavir 1000/100 mg twice daily, n = 34; 1600/100 mg once daily, n = 26; 2000/100 mg once daily, n = 17) from five studies were combined, presented as twice- and once-daily percentiles (P10-P90) and compared. At percentiles where trough concentrations fell below the alleged minimum effective concentration (MEC; 100 ng/mL), the length of time below MEC was determined. RESULTS: Saquinavir concentrations were below MEC at P10 for 0.7 h for twice-daily saquinavir/ritonavir when compared with 8.6 and 6.6 h for 1600/100 and 2000/100 mg once daily, respectively. At P25, 1600/100 mg once daily produced suboptimal concentrations for 5.5 h in contrast to 0.5 h for 2000/100 mg once daily. CONCLUSIONS: Here, we provide substantive data that indicate once-daily saquinavir, in particular 1600/100 mg, is not as robust as the twice-daily regimen based on a population of UK patients; this raises concern over late or missed doses. However, pharmacokinetic data can only ever be a guide to the impact on long-term efficacy.

Published 16 June 2008 in J Antimicrob Chemother, 62(1): 161-7.
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