Taking low-dose ritonavir (Norvir) at the same time as each dose of saquinavir (Invirase) is necessary to achieve optimal saquinavir absorption, according to a small pharmacokinetic study presented yesterday at the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy in Washington.
A small dose of ritonavir is used to boost the blood levels of saquinavir and improve viral suppression. However, ritonavir boosting increases the incidence of side-effects, including diarrhoea, abdominal pain, nausea and vomiting.
Investigators wished to assess the effect of reducing the frequency of ritonavir co-administration on saquinavir levels in people taking both drugs, to reduce the cost and side-effects of anti-HIV therapy. However, they found that omitting ritonavir caused a significant drop in saquinavir levels.
“Withholding a ritonavir dose had a significant impact on saquinavir absorption half-life and overall exposure,” remarked the investigators. “These data confirm the role of ritonavir in enhancing saquinavir exposure and the need to administer saquinavir and ritonavir simultaneously, whether twice daily or once daily.”
Eighteen HIV-positive patients taking hard gel saquinavir / ritonavir 1000/100mg twice daily were recruited for the study, with a median CD4 cell count of 428 cells/mm3. The levels of saquinavir in the blood were measured after the morning dose of boosted saquinavir on the first day, and again on day 2, when ritonavir was omitted. The drugs were given with a meal containing 20g fat on both days.
Concentration-time profiles of saquinavir were taken on day 1 (0 - 12 hours) and of ritonavir on day 2 (12 - 24 hours).
The mean total exposure to saquinavir was 33% lower when ritonavir was omitted (means: 9590 vs. 14,400ng.h/ml; 95% confidence interval [CI]: 4%, 47%). This was paralleled by a 33% decrease in the absorption half-life of the drug (95% CI: 8%, 41%).
However, omitting ritonavir did not cause a significant change in the peak or trough blood concentrations of saquinavir, or in the elimination half-life of the drug. No side-effects were reported on either day of the study.
Boffito M et al. Simultaneous administration of saquinavir hard gel (SQV-hg) and ritonavir (RTV) is required for optimal SQV absorption. 44th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, abstract A-453, 2004.