Study of the interactions between ketoconazole and isoniazid in human volunteers

ABSTRACT

An interaction study between ketoconazole [antifungal agent] and isoniazid [antitubercular agent] was made in ten healthy human volunteers [male] of the age 20 - 30 years and weight 54 - 72 kgs. The blood sampling was done at different time intervals after dosing isoniazid alone and in combination with ketoconazole. The samples were centrifuged and the serum separated was stored [-20°C] for analysis. HPLC was used to determine the serum concentrations of isoniazid. The effect of ketoconazole on the pharmacokinetic parameters [AUC, Cmax t1/2 Ke, Ka and tmax] of isoniazid was investigated. A 50% reduction in the value of area under serum concentration - time curve [AUC] of isoniazid was observed when it was concurrently administered with ketoconazole. The value of Cmax and Ke were also reduced significantly [p<0.05], while elimination half life [t1/2] of isoniazid was increased significantly [p<0.05]. Differences in the values of K2 and tmax were found to be insignificant