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The Effects of Chronic Oral Diltiazem and Cimetidine Dosing on the Pharmacokinetics and Negative Dromotropic Action of Intravenous and Oral Diltiazem in the Dog by Chaiyasit Maskasame; Susan Lankford; Stephen A. Bai is a Medicine article available to read on EtoBox.

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The kinetics and negative dromotropic action of intravenous (1 mg kg-') and oral (5 mg kg-') diltiazem were studied in dogs after acute doses, after treatment for 3 days with oral diltiazem (5 mg kg-I, t.i.d.), and after 3 days' treatment with oral diltiazem (5 mg kg-' t.i.d.) and cimetidine (200mg t.i.d.). Plasma concentrations of diltiazem and two of its metabolites, desacetyldiltiazem and desmethyldiltiazem were measured by HPLC. Chronic oral dosing significantly lowered both the systemic and oral clearance of diltiazem, with no changes in either the volume of distribution or blood binding of diltiazem. Cimetidine treatment resulted in a significant reduction in diltiazem oral clearance from chronic control with no effect on its systemic clearance. The AUCs of both metabolites increased by greater than threefold from acute to chronic oral dosing; however, the ratio of each metabolite's AUC to that of diltiazem AUC was not significantly altered. Cimetidine treatment significantly lowered these ratios. The negative dromotropic potency of diltiazem after the acute oral dose was three times greater than that after intravenous or chronic control dosing. Cimetidine treatment resulted

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Author

Chaiyasit Maskasame; Susan Lankford; Stephen A. Bai

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley (ISSN 0142-2782)

Published

1992

Language

EN

ISBN

9782510130705

Field

Medicine (Health Sciences)