Ritonavir 100 mg · Hard-gelatin capsules

Ritonavir is an antiretroviral drug [see Microbiology (12.4)].

The pharmacokinetics of ritonavir have been studied in healthy volunteers and HIV-infected patients (CD4 greater than or equal to 50 cells per μL). See Table 4 for ritonavir pharmacokinetic characteristics.

Absorption — The absolute bioavailability of ritonavir has not been determined. After a 100 mg tablet dose of ritonavir, peak concentrations of ritonavir were achieved approximately 3 hours and 4 hours after dosing under fasting conditions and moderate-fat (857 KCal; 31% fat, 13% protein, and 56% carbohydrate) meal, respectively.

Effect of Food on Oral Absorption — The bioavailability of ritonavir tablet and oral powder is decreased under fed conditions as compared to fasted conditions.

Following the administration of a 100 mg tablet dose of ritonavir, Cmax and AUCinf of ritonavir were decreased by 21% to 23% under moderate fat (857 Kcal, 30% from fat) or high fat conditions (917 Kcal, 60% calories from fat) relative to fasting conditions.

Following the administration of a 100 mg dose of ritonavir oral powder, Cmax and AUCinf of ritonavir were decreased by 23% to 49% under moderate fat (617 Kcal, 29% calories from fat) or high fat conditions (917 Kcal, 60% calories from fat) relative to fasting conditions.

Metabolism — Nearly all of the plasma radioactivity after a single oral 600 mg dose of 14C-ritonavir oral solution (n = 5) was attributed to unchanged ritonavir. Five ritonavir metabolites have been identified in human urine and feces. The isopropylthiazole oxidation metabolite (M-2) is the major metabolite and has antiviral activity similar to that of parent drug; however, the concentrations of this metabolite in plasma are low. In vitro studies utilizing human liver microsomes have demonstrated that cytochrome P450 3A (CYP3A) is the major isoform involved in ritonavir metabolism, although CYP2D6 also contributes to the formation of M–2.

Elimination — In a study of five subjects receiving a 600 mg dose of 14C-ritonavir oral solution, 11.3 ± 2.8% of the dose was excreted into the urine, with 3.5 ± 1.8% of the dose excreted as unchanged parent drug. In that study, 86.4 ± 2.9% of the dose was excreted in the feces with 33.8 ± 10.8% of the dose excreted as unchanged parent drug. Upon multiple dosing, ritonavir accumulation is less than predicted from a single dose possibly due to a time and dose-related increase in clearance.

Gender, Race and Age — No age-related pharmacokinetic differences have been observed in adult patients (18 to 63 years). Ritonavir pharmacokinetics have not been studied in older patients.

A study of ritonavir pharmacokinetics in healthy males and females showed no statistically significant differences in the pharmacokinetics of ritonavir. Pharmacokinetic differences due to race have not been identified.