PHARMACOLOGIC INTERACTIONS OF ALBUTOIN WITH OTHER ANTICONVULSANT DRUGS

¹ Department of Pharmacology, Baxter Laboratories, Inc., Morton Grove, Illinois

The isobole method was used to evaluate the acute anticonvulsant and toxic interactions of albutoin paired with phenobarbital, diphenyhhydantoin or trimethadione and of phenobarbital paired with diphenylhydantoin. Anticonvulsant potencies (EDSO) of all drugs and of drug pairs in various proportions were determined, after oral administration in male CF-1 mice, by the Metnazol seizure threshold and maximal electroshock seizure tests. Median i.p. lethal doses of all drugs and drug pairs in various proportions were also determined. The potencies of four of the drug pairs were greater than additive (P > .05): trimethadione plus albutoin and diphenyihydantoin plus albutoin in the Metrazol seizure threshold test; phenobarbital plus albutoin and phenobarbital plus diphenylhydantion dantoin in the maximal electroshock seizure test. The potencies of all other drug pairs and the toxicities of all but one pair were not significantly different from additive. Combinations of diphenylhydantoin plus phenobarbital were antagonistic with respect to lethality. The study suggests no pharmacologic incompatibilities based on potency or toxicity for any of the drug pairs studied.