Vehicle effects on activity of an anticonvulsant compound.
The effect of several lipid and nonlipid pharmaceutical solvents on the in vivo activity of 1-diphenylmethyl-4- [(6 methyl-2-pyridyl) methyleneamino] piperazine (I) was evaluated in the mouse. The intensity of onset and the duration of anticonvulsant activity of the compound were affected depending on th type and form of liquid dosage preparation used. The rate of decline in anticonvulsant activity in the 80-20% response range followed apparent zero-order kinetics. A linear relationship between the observed ED50 and the concentration of sorbitol in the dosage form of I was observed. A reduction in the sorbitol content of the dosage form resulted in a proportional increase in the rapidity of onset and the duration of anticonvulsant activity of I. Emulsification restored both the onset and duration of pharmacological activity, which was virtually arrested when the compound was given orally as a solution in oil.
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004655:Emulsions; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D014677:Pharmaceutical Vehicles / Q000494:pharmacology*; D010879:Piperazines / Q000008:administration & dosage* / Q000627:therapeutic use; D011725:Pyridines / Q000008:administration & dosage* / Q000627:therapeutic use; D012640:Seizures / Q000517:prevention & control; D012996:Solutions; D013012:Sorbitol / Q000494:pharmacology; D013535:Suspensions; D013997:Time Factors
D000927:Anticonvulsants; D004655:Emulsions; D014677:Pharmaceutical Vehicles; D010879:Piperazines; D011725:Pyridines; D012996:Solutions; D013535:Suspensions; D013012:Sorbitol