Isoniazid is a mechanism-based inhibitor of cytochrome P450 1A2, 2A6, 2C19 and 3A4 isoforms in human liver microsomes

  title={Isoniazid is a mechanism-based inhibitor of cytochrome P450 1A2, 2A6, 2C19 and 3A4 isoforms in human liver microsomes},
  author={Xia Wen and Jun-sheng Wang and Pertti J. Neuvonen and Janne T. Backman},
  journal={European Journal of Clinical Pharmacology},
Abstract.Objective: In order to evaluate the inhibitory effects of isoniazid on cytochrome P450 (CYP) mediated drug metabolism, the in vitro inhibitory potency and specificity as well as the reduced nicotinamide adenine dinucleotide phosphate (NADPH)-, time- and concentration dependency of isoniazid as an inhibitor of the activity of the major human CYP isoforms were studied. Methods: Using pooled human liver microsomes, the in vitro inhibitory effects of isoniazid on CYP1A2 (phenacetin O… Expand
An evaluation of potential mechanism-based inactivation of human drug metabolizing cytochromes P450 by monoamine oxidase inhibitors, including isoniazid.
Data are consistent with mechanism-based inactivation of human drug-metabolizing CYP enzymes and suggest that impaired metabolic clearance may contribute to clinical drug-drug interactions with some MAO inhibitors. Expand
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The results suggest that the metabolism of medicines which are substrates for CYP2C9 may be altered by PFOS in human bodies, and that PFOS is a mechanism-based inhibitor of CYP 2A6. Expand
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It appears that the chemical properties of a drug critical to CYP3A4 inactivation include formation of reactive metabolites by CYP isoenzymes, preponderance of CYP inducers and P-glycoprotein (P-gp) substrate, and occurrence of clinically significant pharmacokinetic interactions with coadministered drugs. Expand
Inhibitory effect of antituberculosis drugs on human cytochrome P450-mediated activities.
The results suggested that pyrazinamide and ethionamide did not seem to cause drug interactions mediated by the inhibition of CYP, and isoniazid might contribute to the severe drug interactions by a different inhibitory mechanism depending on each of the CYP isozymes, in addition to the reported observations. Expand
More potent inhibition of human CYP2A6 than mouse CYP2A5 enzyme activities by derivatives of phenylethylamine and benzaldehyde
Data from a rapid 96-well plate assay method was developed and validated to measure liver microsomal coumarin 7-hydroxylation in vitro and novel potent inhibitors were found for CYP2A6 and, except for 4-methoxybenzaldehyde, all the compounds inhibited CYP 2A5 and CYP1A6 enzymes differentially. Expand
Evaluation of metabolism dependent inhibition of CYP2B6 mediated bupropion hydroxylation in human liver microsomes by monoamine oxidase inhibitors and prediction of potential as perpetrators of drug interaction.
It is demonstrated that MAO inhibitors can inactivate human liver microsomal CYP2B6 and Caution is required while co-administering phenelzine with substrates that are exclusively metabolized by CYP 2B6 enzyme and substrate that have narrow therapeutic index. Expand
Clinically Important Drug Interactions Potentially Involving Mechanism-based Inhibition of Cytochrome P450 3A4 and the Role of Therapeutic Drug Monitoring
To minimize drug-drug interactions involving mechanism-based CYP3A4 inhibition, it is necessary to choose safe drug combination regimens, adjust drug dosages appropriately, and conduct therapeutic drug monitoring for drugs with narrow therapeutic indices. Expand
Mechanism-Based Inactivation of Human Cytochrome P 4502 C 8 by Drugs in Vitro
Studies were conducted to evaluate the potential mechanismbased inactivation of recombinant and human liver microsomal CYP2C8 by clinically used drugs. Several tricyclic antidepressants, calciumExpand
Mechanism-Based Inactivation of Human Cytochrome P4502C8 by Drugs in Vitro
Several tricyclic antidepressants, calcium channel blockers, monoamine oxidase inhibitors, and various other known CYP3A4 inhibitors exhibited greater inhibition of CYP2C8 (paclitaxel 6α-hydroxylation) following preincubation, consistent with mechanism-based inactivation. Expand