Comparison of bioavailability for phenytoin products prepared by wet granulation in normal subjects and epileptic patients.
A 20% phenytoin (PHT) plain mixture with excipients (20%PM) and three PHT products prepared by wet granulation, which are 20% fine granule (20%FG), 99% air-dried fine granule (99%FG-A) and 99% freeze-dried fine granule (99%FG-F), were prepared. The extents of PHT absorption from these products and the Aleviatin Fine Granules (97%FG) prepared with microcrystalline PHT powder were compared with those from commercially available PHT powder (Aleviatin) and tablet (Hydantol Tablet 25 mg), which are of the Pharmacopoeia of Japan grade, in healthy adult volunteers. In single dose study, the extents of PHT absorption from the powder, 20%PM, 20FG, 99%FG-A, 99%FG-F, 97%FG and tablet were 89.7, 92.2, 99.0, 96.7, 99.1, 99.1 and 99.3%, respectively. The property of almost complete absorption of PHT from the product was shown in the 20%FG, 99%FG-F and 97%FG similar to the tablet. In multiple dose study, the minimum and the average estimated free concentrations of PHT at steady-state for 99%FG-F and 97%FG were nearly equal to those for the tablet, and were higher than those for the powder. In epileptic patients, the plasma PHT concentrations were increased when dosage form was changed from the powder to 99%FG-F. However, the plasma PHT concentrations were scarcely altered when dosage form was changed from the tablet to 99%FG-F. The change in dosage forms from the tablet to 99%FG-F and 97%FG or opposite direction can be done without causing toxicity in epileptic patients, so long as these products are used at the same amounts as PHT.
D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000378:metabolism*; D005243:Feces / Q000032:analysis; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D010672:Phenytoin / Q000008:administration & dosage* / Q000378:metabolism; D011208:Powders; D012463:Saliva / Q000032:analysis; D013607:Tablets
D011208:Powders; D013607:Tablets; D010672:Phenytoin