Effects of subjects' sex, and intake of tobacco, alcohol and oral contraceptives on plasma phenytoin levels.

1. Steady state plasma phenytoin levels in 210 epileptic patients were studied by computerized analysis of covariance to determine whether the subject's sex, alcohol intake, tobacco smoking or use of oral contraceptives influenced the relation between plasma drug level and drug dose. 2. Sex, tobacco smoking and alcohol usage had no statistically significant effect. There was a trend towards higher phenytoin levels relative to drug dose in oral contraceptive users. 3. This finding prompted an additional study of plasma phenytoin levels in 40 oral contraceptive users and 135 aged matched non-users. Analysis of covariance again showed higher plasma phenytoin levels relative to drug dose in users of oral contraceptives (P = 0.061). 4. This finding raised the possibility that the relation between plasma phenytoin level and drug dose differed between males and females who did not use oral contraceptives. However, when the relation between plasma phenytoin levels and drug dose was compared in 159 females who did not use oral contraceptives and 101 males (both groups aged 15 to 70 years) no statistically significant difference was found.