Isoniazid metabolism and hepatotoxicity - ScienceDirect
2016年9月1日 · The major pathways of INH metabolism (Fig. 1) include: (1) Acetylation to form AcINH through N-acetyltransferase (NAT) 2; and (2) Hydrolysis to produce isonicotinic acid (INA) and Hz through amidase. AcINH can also be hydrolyzed to form INA and AcHz.
Identification of a mycobacterial hydrazidase, an isoniazid …
2023年5月20日 · There exists decades-old evidence that some mycobacteria, including Mycobacterium avium and Mycobacterium smegmatis, produce hydrazidase, an enzyme that can hydrolyze the first-line antitubercular...
PharmGKB Summary: Isoniazid Pathway, Pharmacokinetics (PK)
Isoniazid (isonicotinic acid hydrazide, INH; PubChem ID 3767) is a first-line anti-mycobacterial agent used to treat active or latent tuberculosis (TB) infections generated by Mycobacterium tuberculosis [2–4].
Clinical perspectives of isoniazid-induced liver injury
2021年6月1日 · INH metabolism through these hydrolysis pathways is significantly increased in slow acetylators, 80 especially in association with RIF co-treatment. 30 CYP2E1 has been thought to be critical in Hz bioactivation to produce reactive derivatives/metabolites with greater toxicity, and subjects with CYP2E1 c1/c1 alleles and higher enzymatic activity ...
Isoniazid: metabolic aspects and toxicological correlates
Their formation is the result of hydrolysis (INA, HZ), cytochrome P450 (CYP)-dependent oxidation (HZ, NH (3), oxidizing free radicals), and N-acetyltransferase (NAT) activity (AcINH, AcHZ, DiAcHZ). Doubts remain about isonicotinamide (INAAM) as an INH metabolite in mammals.
Role of hydrazine in isoniazid-induced hepatotoxicity in a …
2008年5月15日 · Acetylhydrazine was the first hepatotoxic reactive metabolite proposed for isoniazid (Mitchell et al., 1976). Hydrazine formation can be produced both directly (amidase-catalyzed hydrolysis of isoniazid) or indirectly (amidase-catalyzed hydrolysis of acetylhydrazine).
Isoniazid: the magic molecule | Medicinal Chemistry Research
2012年1月24日 · The hydrolysis in a water–acetonitrile solution of the most active compounds was investigated. The half-time of the degradation was determined from the hydrolysis curve. The rate of hydrolysis of the new products was found to depend on the fragments involved in …
Mechanism of isoniazid‐induced hepatotoxicity: then and now
If hydrolysis led to AcHz and isonicotinic acid, no covalent binding of the pyridine ring would occur. In addition, the characteristics of the liver toxicity in these studies were different from that in humans. In particular, it was an acute rather than a delayed onset idiosyncratic liver injury.
Quantitative Analysis of Isoniazid and Its Four Primary …
2022年12月6日 · Isoniazid, acetylisoniazid, and isonicotinic acid were directly analyzed, whereas hydrazine and acetylhydrazine were determined after derivatization using p-tolualdehyde. Chromatographic separation was conducted on reversed-phase C18 columns with gradient elution, and detection was carried out in multiple reaction monitoring mode.
(PDF) Isoniazid metabolism and hepatotoxicity - ResearchGate
2016年8月1日 · Isoniazid (INH) is highly effective for the management of tuberculosis. However, it can cause liver injury and even liver failure. INH metabolism has been thought to be associated with...