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Oral loading doses of phenytoin were estimated from a simplified pharmacokinetic model. Twenty patients were administered a calculated average dose of 19.1 mg per kilogram of phenytoin divided into two to four increments given over 3 to 21 hours (10.55 +/- 4.74, mean +/- SD). Plasma samples drawn 2 to 22 hours (10.75 +/- 4.32, mean +/- SD) after completion of the loading dose resulted in therapeutic levels ranging from 8.1 to 18.0 microgram per milliliter (11.42-11.37 +/- 2.41, mean +/- SD). Thus, this regimen in which no increment of the loading dose exceeds 600 mg is sufficient to achieve and maintain therapeutic plasma concentrations 18 to 24 hours after initiation of the loading dose.
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