Bioavailability of ACC-9653 (phenytoin prodrug).
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.
Browne
T R
TR
Department of Neurology, Boston University School of Medicine, Massachusetts.
Davoudi
H
H
Donn
K H
KH
Dougherty
C L
CL
Dukes
G E
GE
Evans
B
B
Evans
J E
JE
Jamerson
B
B
Kres
J
J
McEntegart
C M
CM
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
D011355:Prodrugs; D010672:Phenytoin; C043114:fosphenytoin