Sulfonamide-specific haptens during, sulfonamide therapy

Given the involvement of the immune system in sulfonamide (sulfa) adverse reactions, haptens may be important in these reactions. To explore the role of drug haptens, sulfamethoxazole (SMX) -specific antibodies were raised in New Zealand white rabbits. Rabbits were immunized with SMX and adjuvant and antibody harvested. Western blots were run using anti-rabbit primary and goat secondary antibodies. We detected a 42 kD and 100 kD band in the serum of 14 controls who were treated with SMX-TMP for 10 days; samples being obtained at 0, 3, 7 and 14 days. This band was most pronounced on day 3 with density fading notably by day 10. SMX-hydroxylamine was detected by reverse-phase HPLC in urine of these volunteers in concentrations at day 3 from 3 ± 2% of the original sulfa dose. In contrast to the 42 and 100 kD band, the relative concentration of hydroxylamine increased over the course of therapy, reaching highest relative concentration at day 12. This suggests that sulfa-specific haptens may play a role in sulfa hypersensitivity reactions; there does not appear to be a direct relationship between metabolism to reactive metabolites and production of sulfa-specific haptens.