DIPHENYLHYDANTOIN HALF‐LIFE IN MAN AND ITS INHIBITION BY PHENYLBUTAZONE: THE ROLE OF GENETIC FACTORS

Abstract

Abstract The diphenylhydantoin serum half‐life (DPH T /2) has been determined in 14 pairs of healthy young male twins, 7 identical and 7 fraternal. The mean intrapair variance was significantly less in identical than in fraternal twins, indicating that the individual variability in DPH T /2 is mainly due to genetic factors. A daily dose of 100 mg phenylbutazone for 5 or 6 days to 11 pairs of the twins greatly prolonged the DPH T /2. A significant correlation between the prolongation of the DPH T /2 and the serum phenylbutazone levels was found ( r = + 0.586, p <0.01). Nevertheless large individual variations in the prolongation of DPH T /2 at identical phenylbutazone levels were demonstrated. There was, however, no difference in the mean intrapair variance of identical and fraternal twins and we conclude that the individual variability in the extent of impairment of DPH metabolism by phenylbutazone cannot be attributed to genetic influence.