title: Comparisons of oxidative metabolism and reductive capacity in sulfonamide-tolerant and -intolerant patients with human immunodeficiency virus.
abstract: Hypersensitivity reactions to trimethoprim/sulfamethoxazole occur with a high frequency in human immunodeficiency virus (HIV)-infected patients. This study tested whether differences in oxidative metabolism and plasma reductive capacity correlate with sulfonamide intolerance in patients with HIV. Eighteen stable outpatients with HIV were prospectively studied. Nine patients had documented histories of hypersensitivity reactions to trimethoprim/sulfamethoxazole and nine did not. Urinary caffeine metabolite ratios assessed the activity of two oxidative enzymatic pathways: cytochrome P-450 1A2 (demethylation) and 8-hydroxylation. Plasma cyst(e)ine was used as a measure of reductive capacity. The trimethoprim/sulfamethoxazole-intolerant group showed greater rates of 8-hydroxylation, lower rates of demethylation, and lower cyst(e)ine levels. The results of this pilot study extend previous observations of differences in oxidative metabolism and reductive capacity that exist within the population of HIV-infected individuals. In addition, these findings lay the groundwork for future interventional studies that could use agents to inhibit sulfonamide oxidation and increase reductive capacity in sulfonamide-intolerant patients with HIV when rechallenged with trimethoprim/sulfamethoxazole.
authors.affiliation: Department of Medicine, State University of New York Health Science Center at Syracuse, USA.
authors.forename: D F
authors.initials: DF
authors.lastname: Lehmann
authors.forename: P D
authors.initials: PD
authors.lastname: Holohan
authors.forename: D C
authors.initials: DC
authors.lastname: Blair
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000009:adverse effects*; D002110:Caffeine / Q000493:pharmacokinetics / Q000652:urine; D003545:Cysteine / Q000097:blood; D004342:Drug Hypersensitivity / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D008297:Male; D010084:Oxidation-Reduction; D010726:Phosphodiesterase Inhibitors / Q000493:pharmacokinetics / Q000652:urine; D010865:Pilot Projects; D011446:Prospective Studies; D013449:Sulfonamides / Q000009:adverse effects*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects
chemical_list: D000890:Anti-Infective Agents; D010726:Phosphodiesterase Inhibitors; D013449:Sulfonamides; D002110:Caffeine; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D003545:Cysteine