Effect of dose on phenytoin absorption

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Abstract
To determine the effect of dose on phenytoin [used to treat grand mal and psychomotor seizure] bioavailability, a single i.v. 15 mg/kg dose, single oral doses of 400, 800 and 1600 mg and 1600 mg in divided doses (400 mg every 3 h) were given to 6 healthy male human subjects. Values of Vmax (maximum elimination rate) and Km (serum concentration at which rate of elimination is 1/2 the maximum rate) from the i.v. dose were used to determine the extent of absorption. No statistically significant difference in extent of phenytoin absorption was detected, the time to reach maximum phenytoin serum concentrations increased from 8.4 h for the 400 mg dose and 13.2 h for the 800 mg dose to 31.5 h for the 1600 mg dose. After the 400, 800 and 1600 mg doses and 1600 mg divided doses, the serum concentration peaks were 3.9, 5.7, 10.7 and 15.3 mg/l. The prolonged, but complete, absorption of large phenytoin doses is due to slow dissolution and continued absorption from the colon. Due to prolonged absorption of phenytoin, it may be necessary to use larger oral than i.v. loading doses to achieve the same maximum phenytoin serum concentrations.

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