The effect of food on ritonavir bioavailability following administration of ritonavir 100 mg film-coated tablet in healthy adult subjects

Abstract

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. MethodsThis 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. Table 1 presents the food effect results of the ritonavir pharmacokinetic parameters following administration of the ritonavir tablet. Summary of resultsRitonavir 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. ConclusionOverall, ritonavir pharmacokinetics after administration of the tablet are slightly affected by meal content (with moderate or high fat).

Effect of meal and antisecretory agents on the pharmacokinetics of danoprevir/ritonavir in healthy volunteers

“…Therefore, the effect of food on T max and C max observed in this study is not considered to be clinically significant because there was no change in DNV C 12h . For ritonavir, the delay in T max and decrease in C max and AUC 0–∞ observed with both low‐ and high‐fat meals were expected and were consistent with the prescribing information for ritonavir 100 mg tablets…”

Shared IVIVR for Five Commercial Enabling Formulations Using the BiPHa+ Biphasic Dissolution Assay

“…Klein et al investigated the pharmacokinetic of 100 mg Norvir ® in 27 healthy human subjects [36]. Xu et al established a level A IVIVR with different ritonavir drug products including a fraction absorbed of 60-80% [8].…”

Biopharmaceutic In Vitro In Vivo Extrapolation (IVIV_E) Informed Physiologically-Based Pharmacokinetic Model of Ritonavir Norvir Tablet Absorption in Humans Under Fasted and Fed State Conditions

“…The ability of the PBPK model to predict the clinically observed food effect was verified by simulating 10 trials with 27 subjects dosed with 100 mg Norvir tablet under the high-fat fed state. 32 The predicted pharmacokinetic parameters AUC 0-t and C max were compared against the observed parameters.…”

“…For statistical comparison of simulated and observed pharmacokinetic parameters, AAFE (average absolute fold error) was calculated as described by Shimizu et al 36 In addition, unpaired student t test was applied to assess the statistical differences between simulated fasted and predicted fed state pharmacokinetic parameters (C max , T max , and AUC 0-t ) obtained by simulation of Ng et al study. 32 Graph Pad Prism software version 8.2 was used for this analysis (GraphPad Software, Inc., San Diego, CA).…”