A PHASE-I EVALUATION OF CONCOMITANT RIFABUTIN AND DIDANOSINE IN SYMPTOMATIC HIV-INFECTED PATIENTS

It has been suggested that didanosine (ddI) may undergo hepatic metabo lism. Rifabutin is an inducer of drug metabolism. Fifteen human immuno deficiency virus-infected patients whose conditions were stabilized on twice-daily doses of ddI participated in a Phase I, open-label, pharm acokinetic and safety drug interaction study between rifabutin and ddI , Twelve patients completed the study. All patients received their reg ular ddI dose (167-375 mg) on day 1. On days 2-13 they received once-d aily rifabutin (600 mg, three patients; 300 mg, nine patients) with th eir regular twice-daily ddI regimen. On days 14-16 they received rifab utin alone. Serial blood and urine samples were collected for 12 h on day 1 and for 24 h on days 13 and 16, and safety evaluations were made throughout the study. Average day 1/day 13 ddI pharmacokinetic ratios and 95% confidence interval values for C-max, AUC(0-x) Cl-5/F, and t( 1/2),lambda(z) were 1.17(0.96-1.38), 1.13(0.99-1.27), 0.91 (0.81-1.01) , and 0.97 (0.791.15), respectively (p > 0.05 for all comparisons; pai red t test), A 20% difference in AUG(0-x) could be detected with 90% p ower. Also, there were no significant changes in laboratory values or electrocardiograms, or in rifabutin pharmacokinetic parameters when th e two agents were coadministered, Based on the safety and pharmacokine tic assessments, rifabutin did not appear to interact with ddI.