PHARMACOKINETIC DRUG-DRUG INTERACTION STUDY OF DELAVIRDINE AND INDINAVIR IN HEALTHY-VOLUNTEERS

The potential pharmacokinetic drug-drug interaction between delavirdin e, a nonnucleoside analogue reverse transcriptase inhibitor, and indin avir, an inhibitor of HIV protease, was evaluated in healthy volunteer s. Subjects received a single 800-mg dose of indinavir sulfate on day 1 (baseline). Delavirdine mesylate 400 mg was administered three times daily on days 2 through 10. On day 9, a single 400-mg dose and on day 10 a single 600-mg dose of indinavir were given along with morning do ses of delavirdine. Pharmacokinetic evaluations of indinavir were made on days 1, 9, and 10, and of delavirdine on days 8, 9, and 10. Fourte en healthy male volunteers completed the study. Single doses of indina vir had no clinically important effects on the pharmacokinetics of del avirdine. Mean indinavir C-max values for the 400-mg and 600-mg doses administered concomitantly with delavirdine were dose proportionally l ower than that observed following the 800-mg dose administered alone. Mean T-max values were similar and ranged from 1.0 +/- 0.3/hour for in dinavir 800 mg administered alone to 1.3 +/- 0.4/hour for indinavir 60 0 mg administered with delavirdine. These results indicate that delavi rdine had no clinically important effect on the rare of indinavir abso rption. In contrast, the mean indinavir AUC(0-infinity) value followin g the 400-mg dose administered with delavirdine was only 14% lower tha n the baseline value de termined for the 800-mg indinavir dose (25,400 +/- 6960 nM hour versus 29,600 +/- 7920 nM hour), and the mean indina vir AUC(0-infinity) value for the 600-mg indinavir dose administered w ith delavirdine (42,700 +/- 9800 nM hour) was 44% greater than the bas eline value. All differences among mean AUC(0-infinity) values were st atistically significant. Mean indinavir half-life values were slightly longer when indinavir was given in a dose with delavirdine than when indinavir was administered alone. These results suggest that delavirdi ne inhibits metabolism of indinavir and support the possibility of a r eduction in the magnitude or frequency of indinavir dosage when given in combination with delavirdine.