| Item |
Information |
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Drug Groups
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approved |
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Description
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Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. [PubChem] |
| Indication |
For the treatment of all forms of tuberculosis in which organisms are susceptible. |
| Pharmacology |
Isoniazid is a bactericidal agent active against organisms of the genus Mycobacterium, specifically M. tuberculosis, M. bovis and M. kansasii. It is a highly specific agent, ineffective against other microorganisms. Isoniazid is bactericidal to rapidly-dividing mycobacteria, but is bacteriostatic if the mycobacterium is slow-growing. |
| Toxicity |
LD50 100 mg/kg (Human, oral). Adverse reactions include rash, abnormal liver function tests, hepatitis, peripheral neuropathy, mild central nervous system (CNS) effects. In vivo, Isoniazid reacts with pyridoxal to form a hydrazone, and thus inhibits generation of pyridoxal phosphate. Isoniazid also combines with pyridoxal phosphate; high doses interfere with the coenzyme function of the latter. |
| Affected Organisms |
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| Biotransformation |
Primarily hepatic. Isoniazid is acetylated by N -acetyl transferase to N -acetylisoniazid; it is then biotransformed to isonicotinic acid and monoacetylhydrazine. Monoacetylhydrazine is associated with hepatotoxicity via formation of a reactive intermediate metabolite when N-hydroxylated by the cytochrome P450 mixed oxidase system. The rate of acetylation is genetically determined. Slow acetylators are characterized by a relative lack of hepatic N -acetyltransferase. |
| Absorption |
Readily absorbed following oral administration; however, may undergo significant first pass metabolism. Absorption and bioavailability are reduced when isoniazid is administered with food. |
| Half Life |
Fast acetylators: 0.5 to 1.6 hours. Slow acetylators: 2 to 5 hours. |
| Protein Binding |
Very low (0-10%) |
| Elimination |
From 50 to 70 percent of a dose of isoniazid is excreted in the urine within 24 hours. |
| External Links |
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