title: Dipyridamole bioavailability in subjects with reduced gastric acidity.
abstract: Dipyridamole (DP) is an antiplatelet agent that shows decreased oral bioavailability with increased gastric pH that occurs with commonly prescribed antacids. An extended-release (ER) formulation of DP that employs tartaric acid to improve bioavailability of DP in the presence of elevated gastric pH was developed as a combination antiplatelet product with immediate-release aspirin. This crossover-designed study examined the relative bioavailability of DP from the composite product compared to conventional DP tablets during reduced gastric acidity. Gastric pH was increased (pH > 4.0) in 20 healthy subjects with lansoprazole (30 mg/d for 5 days). Dipyridamole systemic exposure over 12 hours was compared after oral administration of a single composite ER capsule (200 mg DP + 25 mg aspirin) versus two 100-mg conventional DP tablets given 6 hours apart combined with 81 mg aspirin. DP relative bioavailability was reduced 53% with conventional tablets compared to the composite buffered ER capsule in reduced gastric acid conditions. Peak DP plasma concentrations were 57% lower with immediate-release tablets compared to the composite formulation with high stomach pH. Substituting generic DP plus low-dose aspirin may be less effective than the buffered DP composite product in patients with concomitant antacid therapies.
authors.affiliation: Department of Pharmaceutics, University of Florida, Gainesville, FL, USA.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Derendorf
authors.forename: Cam P
authors.initials: CP
authors.lastname: VanderMaelen
authors.forename: Rolf-Stefan
authors.initials: RS
authors.lastname: Brickl
authors.forename: Tom R
authors.initials: TR
authors.lastname: MacGregor
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Eisert
mesh_terms: D000126:Achlorhydria / Q000378:metabolism*; D000328:Adult; D001241:Aspirin / Q000008:administration & dosage; D001682:Biological Availability; D018592:Cross-Over Studies; D004176:Dipyridamole / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013608:Tablets, Enteric-Coated
chemical_list: D004338:Drug Combinations; D010975:Platelet Aggregation Inhibitors; D013608:Tablets, Enteric-Coated; D004176:Dipyridamole; D001241:Aspirin