Analysis of potential risk factors associated with the development of pancreatitis in phase I patients with AIDS or AIDS related complex receiving didanosine

Authors: Grasela TH, Walawander CA, Beltangady M, Knupp CA, Martin RR, Dunkle LM, Barbhaiya RH, Pittman KA, Dolin R, Valentine FT
Publication: J Infect Dis
Keywords: Acquired Immunodeficiency Syndrome, adverse effects, Age Factors, AIDS-Related Complex, analysis, chemically induced, complications, didanosine, Dose-Response Relationship, drug, drug therapy, gastroenterology, humans, infectious disease, maximum tolerated dose, New York
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Abstract

Phase I dose-escalating trials of didanosine revealed dose-limiting toxicities, including pancreatitis, and established a total daily dose of 12.5 mg/kg/day as the maximum tolerated dose. Clinical and pharmacokinetic data of 61 patients from two trials were analyzed to further evaluate 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, and 15 (50%) of 30 who received > 750 mg/day developed pancreatitis (P < .001). A relationship between risk of pancreatitis and steady-state plasma concentrations of didanosine and age was also observed, suggesting that knowledge of didanosine pharmacokinetics provided additional information regarding risk of toxicity. Further confirmation of these findings will be necessary to determine if the risk factors for pancreatitis remain the same at lower doses currently used.

By, Thaddeus H Grasela, Cynthia Walawander, Beltangady M, Knupp CA, Martin RR, Dunkle LM, Barbhaiya RH, Pittman KA, Dolin R, Valentine FT