An open label bioequivalence study of oral saquinavir (RO 31‐8959) using a stable isotope formulation of saquinavir as an “in vivo” internal standard

This study was designed to compare the relative bioavailabilities of two different formulations of the HIV protease inhibitor, saquinavir. In view of the high intra‐subject variability associated with saquinavir a stable isotope was employed. We predicted a reduction in intra‐subject variability of 40–60% consequently allowing fewer healthy volunteers to be exposed to the trial drug. Bioequivalence testing was performed using the relative AUC (RAUC) and the relative Cmax (RCmax); the ratio of AUC (or Cmax) from the unlabelled capsule dose to the AUC (or Cmax) from the concurrent labelled dose. We expected that the relative pharmacokinetic measures would have a smaller variance than the untransformed pharmacokinetic measures. For RAUC and RCmax bioequivalence was established according to the equivalence criteria (80‐125%). Bioequivalence was also established based on the unlabelled parameters for AUC and Cmax according to the equivalence criteria (80–125%). The estimate of within subject variability (CV) for RAUC was reduced compared to the unlabelled AUC data (27.78% versus 33.74%). On the contrary, the estimate of within subject variability (%CV) for RCmax was higher than for the unlabelled Cmax data (38.32% versus 33.94%). These results indicated that the use of the relative parameter had little impact on the intra‐subject variability contrary to what was predicted. Clinical Pharmacology & Therapeutics (2004) 75 , P83–P83; doi: 10.1016/j.clpt.2003.11.319