The steady-state disposition of indinavir is not altered by the concomitant administration of clarithromycin

Study objectives: To evaluate the safety and potential pharmacokinetic inte raction between indinavir and clarithromycin. Study methods: Ln a randomized, three-period, crossover fashion, 12 healthy adults received the following for 1 week: 800 mg oral indinavir sulfate ev ery 8 hours with placebo, 500 mg oral clarithromycin every 12 hours with pl acebo, and indinavir sulfate with clarithromycin, Plasma indinavir, clarith romycin, and 14-hydroxyclarithromycin concentrations were determined after the last dose in each treatment period. Results: Administration of indinavir sulfate with clarithrompcin caused a s tatistically significant increase in four pharmacokinetic parameters: a 58% increase in plasma indinavir concentrations at 8 hours (P = .029), a 47% i ncrease in values for clarithromycin area under the plasma concentration ve rsus time curve from time zero to the last measured concentration [AUC(0-12 h); P = .0002], and 49% and 48% decreases in 14-hydroxyclarithromycin AUC(0 -12h) and maximum plasma concentration (C-max) values, respectively (P =.00 01 and P =.0001). These effects are not considered to be clinically signifi cant in view of the insignificant effects on the values for indinavir area under the plasma concentration versus time curve from time zero to the last measured concentration [AUC(0-8h)] and C-max as well as the safety profile of clarithromycin. Conclusions: The combination of indinavir sulfate and clarithromycin is gen erally well tolerated and can be coadministered without dose adjustment.