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.
PIP: Computerized analysis of covariance was used to study the steady state plasma phenytoin levels of 210 epileptic patients to determine whether sex, alcohol intake, tobacco smoking, or use of oral contraceptives (OCs) affected the relation between plasms drug level and drug dose. Sex, tobacco, and alcohol had no statistically significant effects. However, a trend toward higher phenytoin levels relative to drug dose in OC users prompted an additional study of plasma phenytoin levels in 40 OC users and 135 aged-matched controls (nonusers). Again, analysis of covariance showed higher plasma phenytoin levels relative to drug dose in OC users (P=.061). This finding was investigated in relation to subjects' sex; however, when the relation between plasma phenytoin levels and drug dose was compared in 159 females who did not use OCs and 101 males (both groups aged 15-70 years), no statistically significant difference was found. Therefore, the results indicate that age (beyond puberty) and sex are not significant determinants of plasma phenytoin levels relative to dose; tobacco use and moderate intake of alcohol were also unimportant considerations; however, the significance of OCs to plasma levels raises the possibility that OC use may decrease phenytoin metabolism.