Pharmacokinetic-Pharmacodynamic Consequences and Clinical Relevance of Cytochrome P450 3A4 Inhibition

  title={Pharmacokinetic-Pharmacodynamic Consequences and Clinical Relevance of Cytochrome P450 3A4 Inhibition},
  author={George K Dresser and John David Spence and David G Bailey},
  journal={Clinical Pharmacokinetics},
Drug interactions occur when the efficacy or toxicity of a medication is changed by administration of another substance. Pharmacokinetic interactions often occur as a result of a change in drug metabolism. Cytochrome P450 (CYP) 3A4 oxidises a broad spectrum of drugs by a number of metabolic processes. The location of CYP3A4 in the small bowel and liver permits an effect on both presystemic and systemic drug disposition. Some interactions with CYP3A4 inhibitors may also involve inhibition of P… 

Clinically Important Drug Interactions Potentially Involving Mechanism-based Inhibition of Cytochrome P450 3A4 and the Role of Therapeutic Drug Monitoring

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Inhibition of Cytochrome P450 3A: Relevant Drug Interactions in Gastroenterology

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Clinical outcomes and management of mechanism-based inhibition of cytochrome P 450 3 A 4

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Clinical outcomes and management of mechanism-based inhibition of cytochrome P450 3A4

A good understanding of CYP3A4 inactivation and proper clinical management are needed by clinical professionals when these drugs are used and predicting the risks for potential drug–drug interactions is needed.

The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects.

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Pharmacokinetic-Pharmacodynamic Drug Interactions with HMG-CoA Reductase Inhibitors

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Effect of Inhibition of Cytochrome P450 Enzymes 2D6 and 3A4 on the Pharmacokinetics of Intravenous Oxycodone

The results of this study indicate that there are no clinically relevant drug interactions with intravenous oxycodone and inhibitors of CYP2D6 and inhibition of both oxidative metabolic pathways via CYP3A4 and 2D6 are inhibited.

Mechanism-Based Inhibition of Cytochrome P450 3A4 by Therapeutic Drugs

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.

Pharmacokinetic Aspects of Treating Infections in the Intensive Care Unit

Hydrophilic anti-infective agents are often eliminated unchanged by renal glomerular filtration and tubular secretion, and are therefore involved in competition for excretion, and there is a risk of nephrotoxicity and neurotoxicity with some cephalosporins and carbapenems.



Inhibition and Induction of Cytochrome P450 and the Clinical Implications

T careful evaluation of potential drug interactions of a new drug candidate during the early stage of drug development is essential, because the smaller the difference between toxic and effective concentration, the greater the likelihood that a drug interaction will have serious clinical consequences.

Differential inhibition of cytochrome P450 isoforms by the protease inhibitors, ritonavir, saquinavir and indinavir.

The HIV protease inhibitors have differential effects on CYP isozymes and there is obvious potential for clinically significant drug interactions particularly with ritonavir.

P-glycoprotein and cytochrome P-450 3A inhibition: dissociation of inhibitory potencies.

Results demonstrate that, although many P-gp inhibitors are potent inhibitors of CYP3A, a varying degree of selectivity is present and the development and use of P-GP inhibitors with minimal or absent CYP2A inhibitory effects should decrease the impact of drug interactions on the therapeutic use of such compounds.

In vitro and in vivo drug interactions involving human CYP3A.

Cytochrome P4503A (CYP3A) is importantly involved in the metabolism of many chemically diverse drugs administered to humans and makes it a major contributor to presystemic elimination following oral drug administration.

The effect of fluconazole on the steady‐state pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine in humans

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An in vitro-in vivo scaling model predicted a decrement of triazolam clearance due to ketoconazole coadministration that was consistent with the 88% decrement in clearance actually observed in vivo.

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