Individual variation in daily dosage requirements for phenytoin sodium in patients with epilepsy

1 Ninety adult patients receiving phenytoin sodium were studied prospectively in an epileptic centre. Serum concentrations of phenytoin under steady state conditions were measured by gas liquid chromatography. When clinically indicated the daily dosage rate was adjusted by 50 mg steps until a serum concentration of 10--20 mg/l was produced. 2 Concentrations within the above range were obtained in 50 patients; the required dosage rate varied from 200--500 mg/day. Twenty-five clinical, biochemical and haematological attributes were recorded for each patient and tested for correlation with dosage requirement. 3 The dosage requirement correlated most strongly (r = 0.57, P less than 0.001) with body surface area. This relationship (approximately 200 mg/day per m2) accounted however for only one third of the total dosage variance. 4 Amongst 18 patients receiving simultaneous treatment with phenobarbitone, the effective plasma clearance of this drug taken in conjunction with body surface area accounted for a significantly greater proportion of the total dosage variance. Multiple regression analysis failed to reveal other, more widely applicable predictors of individual phenytoin dosage requirements.