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Session 62 Poster Session Pharmacokinetics of Antiretroviral Drugs Session Time: 4:30-6:30 pm Room 4E-F

432-W. Comparative Pharmacokinetics and Short-Term Safety of Twice Daily (BID) Fortovase/Ritonavir and Invirase/Ritonavir M. Kurowski*1, T. Sternfeld1, A. Hill2, and C. Moecklinghoff3 1HIV-LAB, Auguste-Viktoria Krankenhaus, Berlin, Germany; 2Roche, Welwyn, UK; and 3Roche, Grenzach, Germany Background: Although the bioavailability of saquinavir (SQV) hard gel (Invirase) is lower than that of SQV soft gel (Fortovase), when combined with ritonavir ® at a dose of SQV/r 400-mg/400-mg BID, bioavailability of SQV from these formulations is similar. SQV/r 1000-mg/100 mg BID is being investigated to minimise the dose-related toxicity of RTV. The aim was to determine the comparative pharmacokinetics, especially the trough concentrations under SQV/r 1000-mg/100-mg BID when SQV is administered using Invirase or Fortovase at steady state. Methods: This was a single-centre, open, prospective, cross-over study. 24 healthy volunteers received SQV/r 1000-mg/100-mg BID for 2 weeks (SQV as Invirase, n=12; SQV as Fortovase, n=12), after which the pharmacokinetic profile of SQV (taken with food) was determined over a 24-hour period. Subjects then crossed to the alternative formulation and the pharmacokinetic profile of SQV was again determined 10 days later. Saquinavir concentrations were determined by a LC/MS method, and statistical tests were based on log transformed data. A 2-sided t-test was performed on the average of 3 consecutive trough values. Results: Mean Cmin values at 12 hours post-dose were significantly higher for Invirase (383±151-ng/mL) than for Fortovase (237±134-ng/mL)(p=0.017). Gastrointestinal adverse events occurred more frequently with Fortovase than with Invirase. Diarrhea was recorded in 18 Fortovase vs 5 Invirase cases. Conclusion: Despite the poor bioavailability of Invirase as a sole protease inhibitor, pharmacokinetic enhancement with 100-mg of ritonavir produced plasma SQV concentrations that exceeded those of boosted Fortovase. Additionally, Invirase appears to be better tolerated than Fortovase.

©2002 9th Conference on Retroviruses and Opportunistic Infections