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Interactions of Phenytoin and Phenobarbital in Terms of Order and Temporal Spacing of Administration in Monkeys
Author(s) -
Lockard Joan S.,
Levy René H.,
Uhlir Vladimir,
Farquhar John A.
Publication year - 1976
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1157.1976.tb04460.x
Subject(s) - phenobarbital , phenytoin , anticonvulsant , dosing , pharmacology , drug administration , medicine , epilepsy , plasma concentration , anesthesia , endocrinology , psychiatry
Summary The present study investigated order and temporal spacing interactions of phenytoin and phenobarbital in terms of plasma levels during multiple dosing in monkeys. Phenytoin at a dose of 30 mg/kg and phenobarbital at a dose of 3 mg/kg were administered separately to 4 animals (control group) by nasogastric intubution daily for 10 days. In four subsequent 10‐day periods the drugs were administered together in 4 other animals (interaction group) at different times of the day (immediately following one another, 1/2 hr apart, and 6 hr apart) and in a different order of administration (either phenobarbital first and phenytoin later, or the reverse). Blood samples were obtained on the 5th, 8th, and 10th day of each 10‐day period. The plasma data indicated: (a) phenytoin is capable of autoinduction, (b) phenobarbital lowers the levels of phenytoin under the four methods of administration studied here, and (c) phenytoin can affect the levels of phenobarbital. The latter interaction is a function of order and temporal spacing of drug administration.