Sulfamethizole‐induced inhibition of diphenylhydantoin, tolbutamide, and warfarin metabolism

Abstract

The influence of sulfamethizole on the metabolism of diphenylhydantoin (DPH), tolbutamide, and warfarin is examined. In 8 patients DPH mean half-life (T/2) increased from 11.8 ± 3.3 hr to 19.6 ± 5.2 hr and mean metabolic clearance rate (MCR) decreasedfram 43.7 ± 16.8 to 28.1 ± 9.1 ml/min during sulfamethizole treatment. In 6 patients mean tolbutamide T/2 increased from 5.7 ± 1.2 to 9.2 ± 1.2 hr MCR decreased from 17.0 ± 5.4 to 10.5 ± 1.2 ml/min. In 2 patients warfarin T/2 increased from an average of 64.7 to 92.7 hr and MCR decreased from 1.65 ml/min to 1.05 ml/min. In 4 patients on long-term DPH treatment after 1 wk on sulfamethizole, there was an increase in serum DPH concentration in 3. It is suggested that sulfamethizole inhibits hepatic metabolism of DPH, tolbutamide, and warfarin.