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Abstract
AbstractNonlethal doses of methylxanthines (caffeine or theophyline) produced dose‐dependent lethality in rats pretreated with isoniazid. Isoniazid pretreatment did not alter theophylline concentration in blood or brain, suggesting that the drug interaction was not due to altered distribution or metabolism of theophylline. Death was associated with tonic‐clonic seizures and pulmonary congestion. The toxicity of the drug combination was blocked by the anticonvulsants diazepam, barbital, and trimethadione, but not by chlorpromazine, a sedative drug which lacks anticonvulsant activity. Thus, there is a fatal drug interaction between isoniazid and theophylline which may be due to convulsions that trigger a shock lung syndrome.
Published Version
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