ANALYSIS OF POTENTIAL RISK-FACTORS ASSOCIATED WITH THE DEVELOPMENT OFPANCREATITIS IN PHASE-I PATIENTS WITH AIDS OR AIDS-RELATED COMPLEX RECEIVING DIDANOSINE

Phase I dose-escalating trials of didanosine revealed dose-limiting to xicities, including pancreatitis, and established a total daily dose o f 12.5 mg/kg/day as the maximum tolerated dose. Clinical and pharmacok inetic data of 61 patients from two trials were analyzed to further ev aluate the risk of pancreatitis: 1 (6.3%) of 16 patients who received <500 mg/day didanosine, 2 (13.3%) of 15 who received 500-750 mg/day, a nd 15 (50%) of 30 who received >750 mg/day developed pancreatitis (P < .001). A relationship between risk of pancreatitis and steady-state pl asma concentrations of didanosine and age was also observed, suggestin g that knowledge of didanosine pharmacokinetics provided additional in formation regarding risk of toxicity. Further confirmation of these fi ndings will be necessary to determine if the risk factors for pancreat itis remain the same at lower doses currently used.