Comparative study of bioavailabilities of different phenytoin preparations.

A comparative study of the serum phenytoin (PHT) concentration levels during the treatment with different PHT preparations (powders or tablets) manufactured by two Japanese pharmaceutical companies gave the following results: 1) The serum PHT concentration levels (S in microgram/ml) of children (aged 7-11) who were taking Company A's powder and phenobarbital were less than 2.0 microgram/ml in 21 out of 24 (87.5%) cases without correlation with the dosage (D in mg/kg). The levels in 19 children of the same ages taking Company A's tablets showed significant correlation with the dosage, and the regression line was S = 1.9D - 2.65 (r = 0.86). 2) In 33 cases, previously administered Company A's powder was substituted with different PHT preparations of the same or a lesser dosage; Company A's tablet in group I; powderized Company A's tablet in group II: Company B's powder in group III; and Company B's tablet (solid or powderized) in group IV. In all cases, the PHT S/D ratio increased after the substitution and the mean increase +/- SD was 1.3 +/- 1.2 (p less than 0.001) for group I, 1.0 +/- 0.1 (p less than 0.001) for group II, 0.45 +/- 0.1 (p less than 0.005) for group III, and 1.6 +/- 0.4 (p less than 0.015) for group IV. 3) Tested in five patients using three specially prepared phenytoin powders with different particle sizes clearly demonstrated the fact that the smaller the PHT particle, the higher the PHT S/D ratio. 4) It was suggested that the factors other than particle size of the drug should be taken into consideration in the interpretation of different bioavailabilities of different PHT preparations.