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

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.

• Authors: T H Grasela, C A Walawander, M Beltangady, C A Knupp, R R Martin, L M Dunkle, R H Barbhaiya, K A Pittman, R Dolin, F T Valentine
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 169 Issue 6 Pg. 1250-5 (Jun 1994) ISSN: 0022-1899 [Print] United States
• PMID: 8195601 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Didanosine

Topics

• AIDS-Related Complex (complications, drug therapy)
• Acquired Immunodeficiency Syndrome (complications, drug therapy)
• Age Factors
• Didanosine (adverse effects, pharmacokinetics, therapeutic use)
• Dose-Response Relationship, Drug
• Humans
• Pancreatitis (chemically induced, complications)
• Risk Factors