Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A by H2‐receptor antagonists

  title={Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A by H2‐receptor antagonists},
  author={Carmen Martı́nez and C. Albet and Jos{\'e} A. G. Ag{\'u}ndez and Eduardo Herrero and Juan Antonio Carrillo and M Marquez and Julio Ben{\'i}tez and Jos{\'e} Alfonso Ortiz},
  journal={Clinical Pharmacology \& Therapeutics},

The effect of cimetidine on dextromethorphan O-demethylase activity of human liver microsomes and recombinant CYP2D6.

Clinically, cimetidine therapy impairs the clearance of various drugs metabolized by CYP2D6, such as desipramine and sparteine. Cimetidine is known to reversibly inhibit CYP2D6 in vitro; however, Ki

Contribution of three CYP3A isoforms to metabolism of R- and S-warfarin.

While all enzymes preferentially metabolized R-warfarin, CYP3A4 was the most efficient at metabolizing all reactions and thus may require lower doses and be at risk for adverse drug-drug interactions related to the contributions of the respective enzymes.

In vitro inhibition of methadone and oxycodone cytochrome P450-dependent metabolism: reversible inhibition by H2-receptor agonists and proton-pump inhibitors.

Omeprazole, esomeprazole and pantoprazoles had greater effects on CYP3A4-mediated reactions, whereas lansoprazole was selective for CYP2D6-mediated formation of oxymorphone.

Effect of sodium ozagrel on the activity of rat CYP2D6.

Functional expression and comparative characterization of four feline P450 cytochromes using fluorescent substrates

The present study suggests the usefulness of the feline CYP recombinant system to obtain chemical affinity information and possible drug interactions in CYP metabolism of domestic cats.

Inhibitory effects of ketoconazole, cimetidine and erythromycin on hepatic CYP3A activities in cats.

In clinical practice, KTZ may result in inhibition based drug-drug interaction with CYP3A substrates in cat patients, whereas CIM and ERY are unlikely to lead to interaction involving CYP1'H and 4-hydroxylation substrates.

Interactions between Over-the-Counter and Illicit Drugs Utilizing Cytochrome P450 Metabolism: Potential for Exacerbation of Pharmacological Response

The findings suggest that in vivo, MA acts as a CYP2D2-inducer, which will lead to altered secondary drug metabolism, increasing the risk of drug-related toxicity.

Drug–Drug Interactions Involving Intestinal and Hepatic CYP1A Enzymes

An up-to-date summary on the expression, regulation, function, and drug–drug interactions of CYP1A enzymes in humans is provided.

Effects of Flos carthami on CYP2D6 and on the Pharmacokinetics of Metoprolol in Rats

CYP2D6 is a risk factor when Flos carthami is administered concomitantly with metoprolol or other CYP2D 6 substrates, and the effects of FlosCarthami on the activity of CYP 2D6 in vivo and in vitro and on the pharmacokinetics of metopolol, in rats are investigated.

Evaluation of Strategies for the Assessment of Drug–Drug Interactions Involving Cytochrome P450 Enzymes

This study gives a representative overview of current methodologies that can be used to study CYP inhibition and suggests the here presented strategy can be applied as a tool during risk evaluation of CYP-mediated DDIs.



Dose-dependent inhibition of CYP1A2, CYP2C19 and CYP2D6 by citalopram, fluoxetine, fluvoxamine and paroxetine

This investigation confirms that paroxetine and fluxetine are potent inhibitors of CYP2D6, that fluvoxamine and fluoxettine are moderate inhibitors of CyP2C19 and that fluVoxamine is a potent inhibitor of CYp1A2 in humans in vivo.

Inhibition by fluoxetine of cytochrome P450 2D6 activity

Inhibition of CYP2D6 activity in patients undergoing treatment with fluoxetine or other serotonin uptake inhibitors could contribute to toxicity or attenuated response from concurrent medications that are substrates of this enzyme.

The polymorphic cytochrome P-4502D6 is involved in the metabolism of both 5-hydroxytryptamine antagonists, tropisetron and ondansetron.

Because these are the major pathways in vivo, coadministration of drugs competing for CYP2D6 and possibly CYP3A4 could influence the human kinetics of tropisetron and ondansetron.

O-demethylation of epipodophyllotoxins is catalyzed by human cytochrome P450 3A4.

It is concluded that catechol formation from teniposide and etoposide is primarily mediated by human CYP3A4, making these reactions susceptible to inhibition by prototypical 3A substrates and inhibitors.

The effect of enzyme inhibition on the metabolism and activation of tacrine by human liver microsomes.

Using cytochrome P450 isoform specific inhibitors CYP1A2 was identified as the major enzyme involved in all routes of THA metabolism and may provide a useful tool for examining the relationship between the metabolism and toxicity of ThA in vivo.

Major pathway of imipramine metabolism is catalyzed by cytochromes P-450 1A2 and P-450 3A4 in human liver.

P-450 1A2 and P-450 3A4 are the major enzymes involved in imipramine N-demethylation in human hepatic microsomes, and these results suggest that interindividual variations in3A4 hepatic content may explain the large variations in imIPramine blood levels observed after uniform dosages and thus explain the variations in clinical efficacy.

The human hepatic cytochromes P450 involved in drug metabolism.

The purpose of this review is to compare and contrast the human P 450s involved in drug metabolism with their related forms in the rat and other experimental species with respect to their relative levels of the various P450s and their metabolic capabilities.

Fluvoxamine Inhibition and Carbamazepine Induction of the Metabolism of Clozapine: Evidence from a Therapeutic Drug Monitoring Service

It is concluded that carbamazepine causes decreased clozapine plasma levels, while fluvoxamine increases the levels.

Clozapine disposition covaries with CYP1A2 activity determined by a caffeine test.

This study suggests that clozapine is metabolised by CYP1A2 to a major extent and no significant relationships with xanthine oxidase and N-acetyl transferase activity, also assessed by a caffeine test, were found.