Pharmacokinetic Properties

Isoniazid is water soluble and is well absorbed when administered either orally or parenterally. Oral absorption is decreased by concurrent administration of aluminum-containing antacids.

Isoniazid does not bind to serum proteins; it diffuses readily into all body fluids and cells, including the caseous tuberculous lesions. The drug is detectable in significant quantities in pleural and ascitic fluids, as well as in saliva and skin. The concentrations in the central nervous system (CNS) and cerebrospinal fluid are generally about 20% of plasma levels but may reach close to 100% in the presence of meningeal inflammation.

Isoniazid is acetylated to acetyl isoniazid by N-acetyl-transferase, an enzyme in liver, bowel, and kidney. Individuals who are genetically rapid acetylators will have a higher ratio of acetyl isoniazid to isoniazid than will slow acetylators. Rapid acetylators were once thought to be more prone to hepatotoxicity, but this is not proved. The slow or rapid acetylation of isoniazid is rarely important clinically, although slow inactivators tend to develop peripheral neuropathy more readily. Metabolites of isoni-azid and small amounts of unaltered drug are excreted in the urine within 24 hours of administration.

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