Pharmacodynamic interactions between isoniazid and theophylline in mice and rats, and the influence of pyridoxine.
Convulsions induced by acute administration of isoniazid (1), theophylline (2) as well as combinations of 1 and 2 were evaluated in male albino mice and male Wistar rats. The effect of pyridoxine (3) on these seizures was tested. Serum and brain levels of 1 after coadministration with 2 and caffeine (4) were assessed. The relevance of the observed pharmacokinetic phenomena in serum is questionable for the CNS processes because animals convulsed late (starting 90 min) and no significant changes of brain levels of 1 were observed. In conclusion, interactions of 1 and 2 may not occur through common mechanisms and exist only if the dose of 1 is toxic suggesting toxicological rather than therapeutic relevance.
Desta
Z
Z
Institute of Pharmacology and Toxicology, Medical Faculty, Leipzig University.
Steingruber
M
M
D000818:Animals; D001921:Brain / Q000378:metabolism; D002110:Caffeine / Q000378:metabolism; D003292:Convulsants / Q000494:pharmacology*; D004347:Drug Interactions; D007538:Isoniazid / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D051379:Mice; D011736:Pyridoxine / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013806:Theophylline / Q000493:pharmacokinetics / Q000494:pharmacology*
D003292:Convulsants; D002110:Caffeine; D013806:Theophylline; D011736:Pyridoxine; D007538:Isoniazid