Bioavailability of ACC-9653 (phenytoin prodrug)

• Published in: Epilepsia (Copenhagen) Vol. 30 Suppl 2; p. S27
• Main Authors: Browne, T R, Davoudi, H, Donn, K H, Dougherty, C L, Dukes, G E, Evans, B, Evans, J E, Jamerson, B, Kres, J, McEntegart, C M
• Format: Journal Article
• Language: English
• Published: United States 01.01.1989
• Subjects: Biological Availability; Clinical Trials as Topic; Humans; Phenytoin - administration & dosage; Phenytoin - analogs & derivatives; Phenytoin - metabolism; Prodrugs - administration & dosage; Prodrugs - metabolism; Random Allocation
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1111/j.1528-1157.1989.tb05822.x

The bioavailability of phenytoin from ACC-9653 versus intravenously administered sodium phenytoin was determined using a crossover design for intravenous and intramuscular administration of ACC-9653 to healthy volunteers. Absolute bioavailability of phenytoin derived from ACC-9653 in each subject was calculated as the ratio of the phenytoin area under the plasma concentration time curve for time 0 to infinity [AUC(0-inf)] after ACC-9653 divided by the phenytoin AUC(0-inf) after intravenous sodium phenytoin. The mean absolute bioavailability of ACC-9653 was 0.992 after intravenous administration and 1.012 after intramuscular administration. These data establish that the bioavailability of ACC-9653 is complete following intravenous or intramuscular administration in single-dose volunteer studies. The absolute bioavailability of phenytoin derived from ACC-9653 in subjects with therapeutic plasma phenytoin concentrations is being studied in patients given simultaneous infusions of stable isotope-labeled tracer doses of ACC-0653 and sodium phenytoin.