14C-Isoniazid (20 mg/kg po or iv) was administered alone or in combination with aspirin (100 mg/kg po), rifampin (30 mg/kg po), ethambutol (100 mg/kg po), or ethanol (3 g/kg po) to rats. In another experiment, phenobarbital sodium (40 mg/kg/day ip) was administered for 3 days prior to isoniazid. Asp
Lethal drug interaction: Isoniazid and methylxanthines
β Scribed by Cynthia M. Harris; Angela C. Springfield; Erik R. Ranschaert; Dr. Harbans Lal
- Publisher
- John Wiley and Sons
- Year
- 1986
- Tongue
- English
- Weight
- 320 KB
- Volume
- 9
- Category
- Article
- ISSN
- 0272-4391
No coin nor oath required. For personal study only.
β¦ Synopsis
Nonlethal doses of methylxanthines (caffeine or theophyline) produced dose-dependent lethality in rats pretreated with isoniazid. lsoniazid 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.
π SIMILAR VOLUMES
The interaction between isoniazid and reducing sugars is acid-catalyzed and reversible. Kinetic studies of hydrazone formation from isoniazid and glucose, lactose, maltose, and galactose have been carried out in simulated gastric juice at 37OC. The forward reaction was found to follow second-order k