PHARMACOKINETIC INTERACTION BETWEEN RITONAVIR AND DIDANOSINE WHEN ADMINISTERED CONCURRENTLY TO HIV-INFECTED PATIENTS

The effect of coadministration of ritonavir and didanosine (ddI) on th e pharmacokinetics of these drugs was investigated in a single-center, three-period, crossover study. Eighteen asymptomatic, HN-positive men were assigned randomly to 6 different sequences of 3 regimens: ddI (2 00 mg every 12 hours) alone for 4 days, ritonavir (600 mg every 12 hou rs) alone for 4 days, and 4 days of ddI with ritonavir under dose-stag gering conditions. Although not statistically significant, ritonavir c oncentrations were slightly higher on average (<10%) with concurrent a dministration of ddI compared with those of ritonavir alone. In contra st, ddI concentrations were lower with concurrent administration compa red with those of ddI alone, maximum concentration and area under the concentration-time curve were reduced by about 15% (p <.05), The ddI e limination rate constant was unaffected by ritonavir, suggesting no ch ange in ddI's systemic metabolism Adverse events were similar between regimens. The relatively minor changes in ritonavir and ddI pharmacoki netics are probably not clinically relevant; therefore, dosage adjustm ent of either compound appears unnecessary when administered concurren tly. However, the combination regimen of ddI and ritonavir continue to be evaluated clinically.