Plasma cysteine deficiency and decreased reduction of nitrososulfamethoxazole with HIV infection.
The aim of these studies was to determine whether HIV-infected patients have a plasma thiol deficiency and whether this is associated with decreased detoxification of the toxic metabolites of sulfamethoxazole. Reduced, oxidized, protein-bound, and total thiol levels were measured in 33 HIV-positive patients and 33 control subjects by an HPLC method utilizing the fluorescent probe bromobimane. The reduction of sulfamethoxazole hydroxylamine and nitrososulfamethoxazole by plasma and the plasma redox balance in the presence of nitrososulphamethoxazole were also determined by HPLC. Reduced plasma cysteine was significantly (p<0.0001) lower in HIV-positive patients (13.0+/-3.0 microM) when compared with control subjects (16.9+/-3.0 microM). Although there was no difference in oxidized, protein-bound, and total cysteine, the thiol/disulfide ratios were lower in HIV-positive patients. Reduced homocysteine was elevated in patients. Plasma from HIV-positive patients was less able to detoxify nitrososulfamethoxazole than control plasma. These findings show that the disturbance in redox balance in HIV-positive patients may alter metabolic detoxification capacity, and thereby predispose to sulfamethoxazole hypersensitivity.
Naisbitt
D J
DJ
Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool L69 3BX, UK.
Vilar
F J
FJ
Stalford
A C
AC
Wilkins
E G
EG
Pirmohamed
M
M
Park
B K
BK
D000328:Adult; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000097:blood* / Q000172:deficiency; D018450:Disease Progression; D004342:Drug Hypersensitivity / Q000209:etiology; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D008875:Middle Aged; D010084:Oxidation-Reduction; D013420:Sulfamethoxazole / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000097:blood
D013438:Sulfhydryl Compounds; C059873:sulfamethoxazole hydroxylamine; C072956:4-nitrososulfamethoxazole; D013420:Sulfamethoxazole; D003545:Cysteine