Related Experiment Video

Updated: May 6, 2026

Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures
10:44

Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures

Published on: March 28, 2017

12.7K

Role of CYP3A in isoniazid metabolism in vivo

Ke Liu1, Feng Li, Jie Lu

  • 1Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh.

Drug Metabolism and Pharmacokinetics
|November 1, 2013
PubMed

Insights

Cytochrome P450 3A (CYP3A) does not significantly impact isoniazid (INH) metabolism or liver injury in mice. Further research is needed to clarify CYP3A's role in INH hepatotoxicity.

Area of Science:

  • Pharmacology
  • Hepatology
  • Drug Metabolism

Background:

  • Isoniazid (INH) is a crucial first-line tuberculosis drug.
  • INH frequently causes liver injury (hepatotoxicity).
  • CYP3A involvement in INH metabolism and toxicity is suspected but not proven.

Purpose of the Study:

  • To investigate the role of Cytochrome P450 3A (CYP3A) in isoniazid (INH) metabolism and hepatotoxicity in vivo.
  • To determine if CYP3A influences INH pharmacokinetics and bioactivation in mice.

Main Methods:

  • Utilized wild-type and Cyp3a-null mice for comparative pharmacokinetic studies.
  • Administered oral isoniazid (50 mg/kg) and analyzed drug and metabolite distribution in liver tissues.
  • Trapped reactive INH metabolites using N-α-acetyl-L-lysine in mouse liver microsomes.

Main Results:

  • No significant differences in INH or acetyl-isoniazid pharmacokinetics were observed between wild-type and Cyp3a-null mice.
  • Similar distribution of INH and its metabolites in the livers of both mouse groups.
  • CYP3A was not found to contribute to the bioactivation pathway of INH, and no liver injury was observed in either group.

Conclusions:

  • CYP3A does not affect the systemic pharmacokinetics of isoniazid in mice.
  • The study did not find evidence for CYP3A's involvement in INH bioactivation or observed hepatotoxicity.
  • Further investigation is required to elucidate the precise mechanisms of CYP3A in INH-induced liver injury.

More Related Videos

Optimized LC-MS/MS Method for the High-throughput Analysis of Clinical Samples of Ivacaftor, Its Major Metabolites, and Lumacaftor in Biological Fluids of Cystic Fibrosis Patients06:14

Optimized LC-MS/MS Method for the High-throughput Analysis of Clinical Samples of Ivacaftor, Its Major Metabolites, and Lumacaftor in Biological Fluids of Cystic Fibrosis Patients

Published on: October 15, 2017

7.3K
An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment08:59

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment

Published on: December 3, 2020

7.3K

Related Concept Videos

Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes01:28

Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes

Cytochrome P450 (CYP450) enzymes are a superfamily of heme-containing monooxygenases that play a pivotal role in Phase I drug metabolism by catalyzing oxidation and reduction reactions.These enzymes transform lipophilic xenobiotics into more hydrophilic metabolites, facilitating subsequent Phase II conjugation and eventual excretion. The CYP450 family is classified into families (e.g., CYP1–CYP3) and subfamilies (e.g., CYP2A, CYP2C), based on amino acid sequence homology.CYP450...
350
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
101
Pharmacokinetics: Drug–Drug Interactions01:25

Pharmacokinetics: Drug–Drug Interactions

Drug interactions occur when the pharmacological effect of one drug is altered by another substance, either enhancing or diminishing its activity. The drug whose activity is altered is known as the object drug, and the substance causing the alteration is called the agent drug or the precipitant. The net effects of these interactions are mostly undesirable, leading to decreased effectiveness or increased adverse effects. In rare cases, interactions can be beneficial, such as the enhanced...
818
Pharmacokinetics in Pediatric Patients: Drug Metabolism01:24

Pharmacokinetics in Pediatric Patients: Drug Metabolism

In pediatric care, understanding the nuances of hepatic drug metabolism is crucial, as it significantly differs from that of adults. This divergence is primarily due to the developmental stage of drug-metabolizing enzymes, which affects how medications are processed in the body. In neonates, for instance, the activity of Phase I enzymes—critical for the initial breakdown of drugs—is markedly reduced, functioning at just 20–40% of the levels seen in adults. This reduction poses...
417
Drug Metabolism: Phase I Reactions01:17

Drug Metabolism: Phase I Reactions

A phase I reaction is a biochemical process that introduces a functionally reactive polar group to a substance. This transformation predominantly occurs in the liver, facilitated by the cytochrome P450 system of hemoproteins situated in the lipophilic endoplasmic reticulum of cells. The metabolite generated through this process can have varying polarities. If it is sufficiently polar, it can be easily excreted in the urine due to its water compatibility. However, if the metabolite is nonpolar,...
5.1K
Drug toxicity: Idiosyncratic Reactions01:16

Drug toxicity: Idiosyncratic Reactions

Idiosyncratic drug reactions represent abnormal chemical responses that vary significantly among individuals, ranging from extreme sensitivity to low doses to insensitivity to high doses. These reactions often occur due to the drug's covalent binding with serum proteins, forming a foreign hapten that triggers an immunotoxicological response. The variability in drug reactions has a strong pharmacogenetic foundation, with genetic differences crucial in how individuals metabolize drugs. For...
232