Purpose of the study

A new 100 mg tablet formulation of ritonavir has been developed that would not require refrigeration. This study compared the single-dose bioavailability of the final ritonavir 100 mg tablet formulation following a moderate-fat or high-fat meal relative to that under fasting conditions.

Methods

This was a single-dose, open-label, 3-period crossover study with a randomized, crossover design. Healthy male and female subjects (n = 27) participated in the study. Serial blood samples were collected for 36 hours after each dose. Ritonavir AUC from time 0 to the last measurable concentration (AUCt) and from time 0 to infinity (AUCinf), maximum plasma concentration (Cmax), and time of Cmax (Tmax) were determined using noncompartmental methods. The bioavailability of the tablet following a meal relative to the fasting condition was assessed by the two one-sided tests procedure using 90% confidence intervals (CI). Safety was assessed throughout the study.

Summary of results

Table 1 presents the food effect results of the ritonavir pharmacokinetic parameters following administration of the ritonavir tablet.

Table 1
Full size table

Ritonavir Cmax and AUC were approximately 20–24% lower when dosed following a meal compared to administration under fasting conditions. The slight difference in Tmax is consistent with delayed gastric emptying following a meal. Overall, the tablet formulation was generally safe and well tolerated.

Conclusion

Overall, ritonavir pharmacokinetics after administration of the tablet are slightly affected by meal content (with moderate or high fat).