Isoniazid clinical pharmacology
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [2]
Clinical Pharmacology
Within 1 to 2 hours after oral administration, isoniazid produces peak blood levels which decline to 50 percent or less within 6 hours. It diffuses readily into all body fluids (cerebrospinal, pleural, and ascitic fluids), tissues, organs, and excreta (saliva, sputum, and feces). The drug also passes through the placental barrier and into milk in concentrations comparable to those in the plasma. From 50 to 70 percent of a dose of isoniazid is excreted in the urine in 24 hours.
Isoniazid is metabolized primarily by acetylation and dehydrazination. The rate of acetylation is genetically determined. Approximately 50 percent of Blacks and Caucasians are “slow inactivators” and the rest are “rapid inactivators”; the majority of Eskimos and Orientals are “rapid inactivators.”
The rate of acetylation does not significantly alter the effectiveness of isoniazid. However, slow acetylation may lead to higher blood levels of the drug and, thus, to an increase in toxic reactions.
Pyridoxine (vitamin B6) deficiency is sometimes observed in adults with high doses of isoniazid and is considered probably due to its competition with pyridoxal phosphate for the enzyme apotryptophanase.
Mechanism of Action
Isoniazid inhibits the synthesis of mycolic acids, an essential component of the bacterial cell wall. At therapeutic levels isoniazid is bacteriocidal against actively growing intracellular and extracellular Mycobacterium tuberculosis organisms.
Isoniazid resistant Mycobacterium tuberculosis bacilli develop rapidly when isoniazid monotherapy is administered.[1]
References
Adapted from the FDA Package Insert.