Pharmacokinetic interactions between isoniazid and theophylline in rats

Pharmacokinetic interactions between isoniazid and theophylline were studied in male Wistar rats, 206 +/- 17 g. Concomitant oral administration of 2 x 5 mg kg-1 isoniazid accelerated slightly the disposition of theophylline (10 mg kg-1, i.v.) whereas 2 x 25 mg kg-1 isoniazid slowed it marginally. The differences in distribution volume, systemic clearance and area under the concentration-time curve (AUC) between the high and the low dose, however, were statistically significant. One week pretreatment with 10 mg kg-1 isoniazid tended towards inhibition (significant decrease of systemic clearance, increase of AUC) and 50 mg kg-1 to acceleration (decrease of half-life, mean residence time and AUC, increase of systemic clearance) of theophylline disposition. After oral pretreatment with 20 mg kg-1 theophylline, neither the kinetics of free isoniazid (50 mg kg-1, i.v.) and the amount acetylated nor the acetylation indices differed from the controls. There was no evidence that concomitant or subacute administration of different doses of isoniazid affects major metabolic pathways of theophylline or that prolonged theophylline treatment interacts with the N-acetylation capacity.