Absorption and Bioavailability: Delavirdine is rapidly absorbed following oral administration, with peak plasma concentrations occurring at approximately one hour. Following administration of delavirdine 400 mg tid (n=67, HIV-1†infected patients), the mean ± SD steady-state peak plasma concentration (C_max) was 35 ± 20 mM (range 2 to 100 mM), systemic exposure (AUC) was 180 ± 100 mM · hr (range 5 to 515 mM · hr) and trough concentration (C_min) was 15 ± 10 mM (range 0.1 to 45 mM). The single-dose bioavailability of delavirdine tablets relative to an oral solution was 85 ± 25% (n=16, non-HIV†infected subjects). The single-dose bioavailability of delavirdine tablets (100 mg strength) was increased by approximately 20% when a slurry of drug was prepared by allowing delavirdine tablets to disintegrate in water before administration (n=16, non-HIV†infected subjects). The bioavailability of the 200 mg strength delavirdine tablets has not been evaluated when administered as a slurry, because they are not readily dispersed in water (see DOSAGE AND ADMINISTRATION).

Delavirdine may be administered with or without food. In a multiple-dose, crossover study, delavirdine was administered every eight hours with food or every eight hours, one hour before or two hours after a meal (n=13, HIV-1†infected patients). Patients remained on their typical diet throughout the study; meal content was not standardized. When multiple doses of delavirdine were administered with food, geometric mean C_max was reduced by approximately 25%, but AUC and C_min were not altered.

Distribution: Delavirdine is extensively bound (approximately 98%) to plasma proteins, primarily albumin. The percentage of delavirdine that is protein bound is constant over a delavirdine concentration range of 0.5 to 196 mM. In five HIV-1†infected patients whose total daily dose of delavirdine ranged from 600 to 1200 mg, cerebrospinal fluid concentrations of delavirdine averaged 0.4% ± 0.07% of the corresponding plasma delavirdine concentrations; this represents about 20% of the fraction not bound to plasma proteins. Steady-state delavirdine concentrations in saliva (n=5, HIV-1†infected patients who received delavirdine 400 mg tid) and semen (n=5 healthy volunteers who received delavirdine 300 mg tid) were about 6% and 2%, respectively, of the corresponding plasma delavirdine concentrations collected at the end of a dosing interval.

Metabolism and Elimination: Delavirdine is extensively converted to several inactive metabolites. Delavirdine is primarily metabolized by cytochrome P450 3A (CYP3A), but in vitro data suggest that delavirdine may also be metabolized by CYP2D6. The major metabolic pathways for delavirdine are N-desalkylation and pyridine hydroxylation. Delavirdine exhibits nonlinear steady-state elimination pharmacokinetics, with apparent oral clearance decreasing by about 22-fold as the total daily dose of delavirdine increases from 60 to 1200 mg/day. In a study of ¹⁴C-delavirdine in six healthy volunteers who received multiple doses of delavirdine tablets 300 mg tid, approximately 44% of the radiolabeled dose was recovered in feces, and approximately 51% of the dose was excreted in urine. Less than 5% of the dose was recovered unchanged in urine. The parent plasma half-life of delavirdine increases with dose; mean half-life following 400 mg tid is 5.8 hours, with a range of 2 to 11 hours.

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