50mg and 100mg ritonavir doses achieve similar levels of saquinavir in Thai patients
There has long been interest in the possibility of reducing the boosting dose of ritonavir from 100 mg to 50 mg. If the boosted PI exposure remains comparable with a lower dose ritonavir, then there will be potential toxicity benefit as well as economic benefit.
This was a PK study conducted in 20 HIV-infected Thai patients stable for at least 3 months on a regimen containing saquinavir/ritonavir (1500/100 mg once daily) plus 2 NRTI with a viral load <50 copies/ml. A 24-hour PK profile was initially obtained when patients were on 1500/100 mg and then subsequently after 7 days on a reduced ritonavir dose (i.e. 1500/50 mg once daily, ritonavir in liquid formulation). There was no difference in saquinavir PK parameters between the 2 PK days, whereas exposure to ritonavir was significantly reduced due to the dose reduction. The short-term reduction in ritonavir did not show a toxicity benefit.
These data are important and highlight the need for a 50 mg ritonavir tablet or capsule rather than the liquid formulation. Additional studies in other patient populations would clearly add weight to the dose reduction strategy.
Van der Lugt J et al. Reducing the boosting dose of ritonavir does not affect saquinavir plasma concentrations in HIV-1-infected individuals. AIDS, 2009, 23(9): 1176-1178.