Pharmacokinetics of isoniazid: The good, the bad, and the alternatives

• Published in: Tuberculosis (Edinburgh, Scotland) Vol. 116; no. S; pp. S66 - S70
• Main Authors: Erwin, Emily R., Addison, Angela P., John, Sarah Finney, Olaleye, Omonike Arike, Rosell, Rosemarie C.
• Format: Journal Article
• Language: English
• Published: Scotland Elsevier Ltd 01.05.2019; Elsevier
• Subjects: Animals; Antitubercular Agents - adverse effects; Antitubercular Agents - pharmacokinetics; Biotransformation; Chemical and Drug Induced Liver Injury - diagnosis; Chemical and Drug Induced Liver Injury - etiology; Chemical and Drug Induced Liver Injury - genetics; Clinical Decision-Making; Drug Substitution; Hepatotoxicity; Humans; Isoniazid; Isoniazid - adverse effects; Isoniazid - pharmacokinetics; Isoniazid metabolism; Patient Selection; Pharmacogenomic Variants; Pharmacokinetics; Risk Assessment; Risk Factors; Toxicokinetics; Tuberculosis; Tuberculosis - diagnosis; Tuberculosis - drug therapy; Tuberculosis - microbiology; Tuberculosis; CYP2E; NAT2; Isoniazid metabolism; GST; Pharmacokinetics; Isoniazid; Hepatotoxicity
• ISSN: 1472-9792; 1873-281X
• DOI: 10.1016/j.tube.2019.04.012

Although isoniazid (INH) has been successful in treating Tuberculosis (TB) since its introduction in 1952, there has been continual reports of drug-associated hepatotoxicity in TB patients. These toxic side effects may reveal more about the recipient of the drug, than the drug itself. A combination of pharmacogenetic and pharmacokinetic studies have identified polymorphisms within enzymes involved in INH metabolism and detoxification. These essential metabolic enzymes include N-acetyltransferase 2, Cytochrome P450 2E1, and glutathione S transferases. Different phenotypes of these enzymes can affect the rate of INH metabolism, resulting in production of hepatotoxic metabolites. This review is intended to elucidate the pharmacokinetics of INH by examining its Administration, Distribution, Metabolism, and Elimination, while suggesting potential alternatives within INH personalized treatment to help reduce hepatotoxicity.