Pharmacokinetic analysis to assess forgiveness of boosted saquinavir regimens for missed or late dosing.
OBJECTIVE
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.
Dickinson
Laura
L
Department of Pharmacology, University of Liverpool, Liverpool, UK. laurad@liv.ac.uk
Boffito
Marta
M
Khoo
Saye H
SH
Schutz
Malte
M
Aarons
Leon J
LJ
Pozniak
Anton L
AL
Back
David J
DJ
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019258:Saquinavir / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D013997:Time Factors; D006113:United Kingdom
D019258:Saquinavir; D019438:Ritonavir