Effect of rifampicin & isoniazid on cytochrome P-450 in mycobacteria.

Geetha Ramachandran; Prema Gurumurthy.

Journal of Medical Research; 2002; 116: 140-144.

Background & objectives : Rifampicin and isoniazid are the most important first line drugs used in the treatment of tuberculosis. These drugs are also used in combination with other medications to treat co-infections. It, therefore, becomes important to study the effect of these drugs on the drug metabolizing system, namely, cytochrome P-450, not only in the host but also in the bacteria. We report the effect of rifampicin and isoniazid on the cytochrome P-450 activity in Mycobacterium smegmatis and M. tuberculosis H37Rv.

Methods : Subinhibitory concentrations of rifampicin and isoniazid were added to the organisms after they had attained the growth phase and cytochrome P-450 activity was estimated in the membranous fractions of the bacteria at different time points.

Results : Rifampicin was able to significantly enhance cytochrome P-450 in both M. smegmatis and M. tuberculosis H37Rv. Isoniazid was found to inhibit cytochrome P-450 in M. tuberculosis H37Rv, while there seemed to be no effect in M. smegmatis .

Interpretation & conclusions : We report here the effect of rifampicin and isoniazid on mycobacterial cytochrome P-450. These findings are similar to those found in eukaryotic organisms. The role of mycobacterial cytochrome P-450 in the metabolism of drugs within the bacteria needs to be elucidated.

Key words : Cytochrome P-450 - isoniazid - mycobacteria - rifampicin

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