title: Bioavailability of ACC-9653 (phenytoin prodrug).
abstract: 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.
authors.affiliation: Department of Neurology, Boston University School of Medicine, Massachusetts.
authors.forename: T R
authors.initials: TR
authors.lastname: Browne
authors.forename: H
authors.initials: H
authors.lastname: Davoudi
authors.forename: K H
authors.initials: KH
authors.lastname: Donn
authors.forename: C L
authors.initials: CL
authors.lastname: Dougherty
authors.forename: G E
authors.initials: GE
authors.lastname: Dukes
authors.forename: B
authors.initials: B
authors.lastname: Evans
authors.forename: J E
authors.initials: JE
authors.lastname: Evans
authors.forename: B
authors.initials: B
authors.lastname: Jamerson
authors.forename: J
authors.initials: J
authors.lastname: Kres
authors.forename: C M
authors.initials: CM
authors.lastname: McEntegart
mesh_terms: D001682:Biological Availability; D002986:Clinical Trials as Topic; D006801:Humans; D010672:Phenytoin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D011355:Prodrugs / Q000008:administration & dosage / Q000378:metabolism*; D011897:Random Allocation
chemical_list: D011355:Prodrugs; D010672:Phenytoin; C043114:fosphenytoin