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Microbiology: Isoniazid is highly active against Mycobacterium tuberculosis which it inhibits in vitro at concentrations of 0.02-0.2 mcg/mL. Isoniazid may have activity against some strains of the mycobacteria including M. kansasii.
Although it is rapidly bactericidal against actively dividing M. tuberculosis, it is considered to be only bacteriostatic against semi-dormant organisms and has less sterilizing activity than rifampicin or pyrazinamide.
Pharmacokinetics: Peak concentrations of about 3-8 mcg/mL appear in blood 1-2 hrs after a fasting dose of 300 mg orally. The rate and extent of absorption of isoniazid is reduced by food. Isoniazid s not considered to be bound appreciably to plasma proteins and diffuses into all body tissues and fluids, including breast milk.
The plasma t½ for isoniazid ranges from about 1-6 hrs, those who are fast acetylators having shorter t½. The primary metabolic route is the acetylation of isoniazid to acetylisoniazid by N-acetyltransferase found in the liver and small intestines. Acetylisoniazid is then hydrolyzed to isonicotinic acid and monoacetylhydrazine; isonicotinic acid is conjugated with glycine to isonicotinyl glycine (isonicotinuric acid) and monoacetylhydrazine is further acetylated to diacetylhydrazine. Some unmetabolized isoniazid is conjugated to hydrazones. The metabolites of isoniazid have no tuberculostatic activity and apart from possibly monoacetylhydrazine, they are also less toxic.
In patients with normal renal function, over 75% of a dose appears in the urine in 24 hrs mainly as metabolites. Small amounts of drug are also excreted in the feces. Isoniazid is removed by dialysis.
