HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:
Sign In to gain access to subscriptions and/or personal tools.

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Request Reprints Citing Articles Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Wijsman, J. A. Articles by Rieder, M. J. Search for Related Content PubMed PubMed Citation Articles by Wijsman, J. A. Articles by Rieder, M. J. Social Bookmarking                         What's this?

Differential Toxicity of Reactive Metabolites of Clindamycin and Sulfonamides in HIV-Infected Cells: Influence of HIV Infection on Clindamycin Toxicity In Vitro

From the Biotherapeutic Group, John P. Robarts Research Institute, London, Ontario, Canada.

Hypersensitivity adverse drug reactions are much more common among patients with acquired immunodeficiency syndrome (AIDS) than in the general population. High rates of hypersensitivity reactions to clindamycin have been noted. To investigate the role of reactive metabolites in these reactions, the authors studied toxicity of clindamycin and sulphamethoxazole (SMX) and their metabolites in uninfected and human immunodeficiency virus (HIV)–infected MOLT3 cells. Infected and uninfected cells were incubated with clindamycin or sulphamethoxazole hydroxylamine in increasing concentrations; reactive metabolites were generated by coincubation of cells and drug with murine microsomes and a microsomal activating system. Over a concentration range of 0 to 400 µM SMX-HA, there was a significant concentration-dependent increase in cell death in HIV-infected compared to uninfected cells (28%±3% vs 8%±5% at 400 µM, P < .05). In contrast, coincubation of cells with clindamycin, microsomes, and a microsomal activating system, as well as combinations of primaquine or pyrimethamine, was not associated with an increase in cell death among infected compared to uninfected cells. No concentration-toxicity was demonstrated. These data support the role of reactive metabolites in adverse drug reactions to sulfonamides during HIV infection, whereas alternate mechanism(s) may be responsible for increased rates of adverse drug reactions to clindamycin among patients with AIDS.

Key Words: Clindamycin • sulphamethoxazole • adverse drug reactions • toxicity • HIV infection • hypersensitivity

Address for reprints: Dr Michael J. Rieder, Division of Clinical Pharmacology, Department of Paediatrics, Children's Hospital of Western Ontario, 800 Commissioner's Road East, London, Ontario, Canada.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?