Trimethoprim, alone or in combination with sulphamethoxazole, decreases the renal excretion of zidovudine and its glucuronide.

Details

Serval ID
serval:BIB_53201DE1F99D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Trimethoprim, alone or in combination with sulphamethoxazole, decreases the renal excretion of zidovudine and its glucuronide.
Journal
British Journal of Clinical Pharmacology
Author(s)
Chatton J.Y., Munafo A., Chave J.P., Steinhäuslin F., Roch-Ramel F., Glauser M.P., Biollaz J.
ISSN
0306-5251 (Print)
ISSN-L
0306-5251
Publication state
Published
Issued date
1992
Volume
34
Number
6
Pages
551-554
Language
english
Notes
Publication types: Clinical Trial ; Journal Article ; Randomized Controlled Trial
Publication Status: ppublish
Abstract
Trimethoprim and trimethoprim-sulphamethoxazole (co-trimoxazole) are often prescribed in HIV patients treated with zidovudine. The pharmacokinetics of zidovudine, after a dose of 3 mg kg-1 by constant rate intravenous infusion over 1 h were evaluated in nine HIV patients in an open, randomized, three-phase crossover study, without and with trimethoprim (150 mg) and trimethoprim-sulphamethoxazole (160 and 800 mg). The metabolic clearance of zidovudine was not significantly influenced by trimethoprim-sulphamethoxazole and trimethoprim. However, the renal clearance of zidovudine was decreased by 58 and 48%, respectively, and that of its glucuronide by 27 and 20% (P < 0.05). The fraction of the dose excreted as the parent compound fell by 47 and 39% and the metabolic ratio by 48 and 43% (P < 0.05). This kinetic drug interaction, apparently due solely to trimethoprim, may only be clinically important when hepatic glucuronidation is also impaired by liver disease or inhibited by other drugs.
Keywords
Adult, Drug Interactions, Female, HIV Infections/drug therapy, Humans, Infusions, Intravenous, Male, Trimethoprim/administration & dosage, Trimethoprim/pharmacology, Trimethoprim-Sulfamethoxazole Combination/administration & dosage, Trimethoprim-Sulfamethoxazole Combination/pharmacology, Zidovudine/administration & dosage, Zidovudine/analogs & derivatives
Pubmed
Web of science
Create date
24/01/2008 13:08
Last modification date
20/08/2019 14:08
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