ReviewClinical pharmacokinetics2003
Factors affecting the clinical development of cytochrome p450 3A substrates.
Review in Clinical pharmacokinetics, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 59 citations in OpenAlex.
- Exploring the relationship between expression of cytochrome P450 enzymes and gefitinib pharmacokinetics.Clinical pharmacokinetics · 2006Trial
- Pharmacokinetics and short-term safety of 873140, a novel CCR5 antagonist, in healthy adult subjects.Antimicrobial agents and chemotherapy · 2005Trial
- High variability of indinavir and nelfinavir pharmacokinetics in HIV-infected patients with a sustained virological response on highly active antiretroviral therapy.Clinical pharmacokinetics · 2005Trial
- Prediction of Pharmacokinetics for CYP3A4-Metabolized Drugs in Pediatrics and Geriatrics Using Dynamic Age-Dependent Physiologically Based Pharmacokinetic Models.Pharmaceutics · 2025Article
- CYP3A Mediates an Unusual C(spAngewandte Chemie (International ed. in English) · 2024Article
- Predicting changes in the pharmacokinetics of CYP3A-metabolized drugs in hepatic impairment and insights into factors driving these changes.CPT: pharmacometrics & systems pharmacology · 2023Article
- Phosphorus-mediated spNature · 2021Article
- Design of novel amyloid β aggregation inhibitors using QSAR, pharmacophore modeling, molecular docking and ADME prediction.In silico pharmacology · 2018Article
- Food and Drug Interactions.Journal of lifestyle medicine · 2017Review
- Population pharmacokinetics of 17α-hydroxyprogesterone caproate in singleton gestation.British journal of clinical pharmacology · 2016Article
- Effect of hepatic function on the EC50 of midazolam and the BIS50 at the time of loss of consciousness.Journal of Zhejiang University. Science. B · 2014Article
- Population pharmacokinetics of cyclosporine A based on NONMEM in Chinese allogeneic hematopoietic stem cell transplantation recipients.European journal of drug metabolism and pharmacokinetics · 2012Article
- Mechanisms underlying food-drug interactions: inhibition of intestinal metabolism and transport.Pharmacology & therapeutics · 2012Review
- Modeling chemical interaction profiles: II. Molecular docking, spectral data-activity relationship, and structure-activity relationship models for potent and weak inhibitors of cytochrome P450 CYP3A4 isozyme.Molecules (Basel, Switzerland) · 2012Article
- Tyrosine kinase inhibitors and drug interactions: a review with practical recommendations.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2012Review
- A computational study of CYP3A4 mediated drug interaction profiles for anti-HIV drugs.Journal of molecular modeling · 2011Article
- Influence of dietary substances on intestinal drug metabolism and transport.Current drug metabolism · 2010Review
- Effect of single and repeat doses of casopitant on the pharmacokinetics of CYP450 3A4 substrates midazolam and nifedipine.British journal of clinical pharmacology · 2010Article
- Structural basis for ligand promiscuity in cytochrome P450 3A4.Proceedings of the National Academy of Sciences of the United States of America · 2006Article
- The influence of cardiovascular physiology on dose/pharmacokinetic and pharmacokinetic/pharmacodynamic relationships.Clinical pharmacokinetics · 2006Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The objective of this review is to evaluate the risks associated with the discovery and development of cytochrome p450 (CYP) 3A substrates. CYP3A is the most abundant p450 enzyme in human liver and is highly expressed in the intestinal tract. The enzyme contributes substantially to metabolism of approximately 50% of currently marketed drugs that undergo oxidative metabolism. As a result, drug-drug interactions involving inhibitors of CYP3A-mediated metabolism can be of great clinical consequence. It is the position of the authors that, because of the factors responsible for the broad substrate specificity of CYP3A, discovery and development of compounds across a large and broad portfolio that are completely devoid of CYP3A metabolism is not feasible. Thus, it is important that scientifically valid approaches to the discovery and development of compounds metabolised by CYP3A be realised. The clinical relevance of CYP3A metabolism is dependent on a multitude of factors that include the degree of intestinal and hepatic CYP3A-mediated first-pass extraction, the therapeutic index of the compound and the adverse event associated with inhibition of CYP3A metabolism. Thus, a better understanding of the disposition of a CYP3A-metabolised compound relative to the projected or observed therapeutic index (or safety margin) can provide ample evidence to support the continued development of a CYP3A substrate. This document will highlight current practices as well as the benefits and risks associated with those practices.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.