Use of isoniazid as a sole agent is, therefore, not advised. No cross resistance with other tuberculostatic drugs Mechanism of resistance is decreased penetration or uptake by the organism. The drug appears to be taken up by an active process and only sensitive organisms contain significant quantities of drug. Isoniazid also inhibits the first Step that is specific for mycolic acid synthesis, a desaturase enzyme. Drug penetrates well into sites of infection, including CSF and center of areas of caseous necrosis.
Elimination is primarily biotransformation and to lesser extent, renal elimination.
There are both fast and slow acetylators, genetically determined. This results in blood levels that vary by a factor of 4 to 6 fold. Slow acetylation predominant phenotype in most Scandinavians, Jews, and North African Caucasians. Drug interaction is more likely with slow acetylators given 'normal' doses. Isoniazid inhibits hepatic mixed function oxidases.