Effects of the Antacids in Didanosine Tablets on Dapsone Pharmacokinetics

doi:10.1059/0003-4819-123-8-199510150-00003

Effects of the Antacids in Didanosine Tablets on Dapsone Pharmacokinetics

From Ottawa General Hospital, Ottawa, Ontario, Canada. Grant Support: By a grant from the Burroughs-Wellcome Positive Action Program, Ontario Ministry of Health. Dr. Cameron is an Ontario Ministry of Health Career Scientist (#02984). Analytical development was supported in part by a grant-in-aid from Wyeth-Ayerst. Requests for Reprints: Jan Sahai, PharmD, Clinical Investigation Unit, Ottawa General Hospital, 501 Smyth Road, Ottawa K1H 8L6, Ontario, Canada. Current Author Addresses: Dr. Sahai: Clinical Investigation Unit, Ottawa General Hospital, 501 Smyth Road, Ottawa K1H 8L6, Ontario, Canada.

Abstract

Objective: To investigate 1) the effects of the magnesium-aluminum antacids in didanosine tablets on dapsone absorption in healthy volunteers and 2) the effects of the antacid formulation of active didanosine tablets on dapsone pharmacokinetics in patients seropositive for human immunodeficiency virus (HIV).

Design: Two separate, randomized, two-period, two-treatment, crossover studies with a 21-day washout period between treatments.

Setting: Clinical investigation unit of a university hospital.

Participants: Six healthy men and six HIV-positive men.

Measurements: Serial dapsone plasma concentrations were measured when dapsone, 100 mg, was administered alone and with either the third of four doses of didanosine placebo tablets (group 1) or the 27th of 28 doses of active didanosine tablets (group 2). In each study, pharmacokinetic variables were determined using noncompartmental methods and compared by analysis of variance.

Results: When dapsone was administered alone, pharmacokinetic variables did not significantly differ from those with dapsone given in either combination (P > 0.10 for all comparisons).

Conclusions: Didanosine, antacids, and other excipients in the currently used didanosine chewable tablets did not significantly affect plasma concentrations of dapsone.