Trial reportEuropean journal of clinical pharmacology2013
Rate of onset of inhibition of gut-wall and hepatic CYP3A by clarithromycin.
Trial report in European journal of clinical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 30 citations in OpenAlex.
- Grapefruit juice markedly increases the plasma concentrations and antiplatelet effects of ticagrelor in healthy subjects.British journal of clinical pharmacology · 2013Trial
- Deconvoluting Gut Versus Liver Cytochrome P450 3A4 Function: Drug Probes, Biomarkers, and Tissue Biopsy.Journal of clinical pharmacology · 2026Review
- Is Rifampin (Rifampicin) Essential for the Treatment of Rhodococcus equi Infections in Foals? A Critical Review of the Role of Rifampin.Journal of veterinary pharmacology and therapeutics · 2025Review
- Drug Interaction PBPK Modeling: Review of the Literature Exposes the Need for Increased Verification of Model Inputs and Outputs as Part of Credibility Assessment.Clinical and translational science · 2025Review
- Pharmacokinetic Model of Drug Interaction of Tacrolimus with Combined Administration of CYP3A4 Inhibitors Voriconazole and Clarithromycin After Bone Marrow Transplantation.European journal of drug metabolism and pharmacokinetics · 2024Article
- Dual Inhibition of CYP3A4 by Voriconazole and Clarithromycin Influences Tacrolimus Pharmacokinetics: Case Series Study.European journal of drug metabolism and pharmacokinetics · 2022Article
- Evidence-Based Guidelines for Drug Interaction Studies: Model-Informed Time Course of Intestinal and Hepatic CYP3A4 Inhibition by Clarithromycin.The AAPS journal · 2021Article
- Irreversible Enzyme Inhibition Kinetics and Drug-Drug Interactions.Methods in molecular biology (Clifton, N.J.) · 2021Article
- The clinical significance of statins-macrolides interaction: comprehensive review of in vivo studies, case reports, and population studies.Therapeutics and clinical risk management · 2019Article
- Drug interactions of meglitinide antidiabetics involving CYP enzymes and OATP1B1 transporter.Therapeutic advances in endocrinology and metabolism · 2018Review
- Clarithromycin, Midazolam, and Digoxin: Application of PBPK Modeling to Gain New Insights into Drug-Drug Interactions and Co-medication Regimens.The AAPS journal · 2017Article
- Drug safety: The concept, inception and its importance in patients' health.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2016Review
- Ritonavir is the best alternative to ketoconazole as an index inhibitor of cytochrome P450-3A in drug-drug interaction studies.British journal of clinical pharmacology · 2015Review
- Effect of Clarithromycin on the Expression of UL16-Binding Protein 2 in Human Cells.Yonago acta medica · 2015Article
- Oral co-administration of elacridar and ritonavir enhances plasma levels of oral paclitaxel and docetaxel without affecting relative brain accumulation.British journal of cancer · 2014Article
- Blood Concentration of Cabazitaxel in a Patient Whose General Condition Worsened with Concomitant Use of Clarithromycin.Case reports in oncologyArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
aimsTo determine the extent and time-course of hepatic and intestinal cytochrome P450 3A (CYP3A) inactivation due to the mechanism-based inhibitor clarithromycin.
methodsIntestinal and hepatic CYP3A inhibition was examined in 12 healthy volunteers following the administration of single and multiple doses of oral clarithromycin (500 mg). Intestinal biopsies were obtained under intravenous midazolam sedation at baseline and after the first dose, on days 2-4, and on days 6-8 of the clarithromycin treatment. The formation of 1'-hydroxymidazolam in biopsy tissue and the serum 1'-hydroxymidazolam:midazolam ratio were indicators of intestinal and hepatic CYP3A activity, respectively.
resultsIntestinal CYP3A activity decreased by 64 % (p = 0.0029) following the first dose of clarithromycin, but hepatic CYP3A activity did not significantly decrease. Repeated dosing of clarithromycin caused a significant decrease in hepatic CYP3A activity (p = 0.005), while intestinal activity showed little further decline. The CYP3A5 or CYP3A4*1B genotype were unable to account for inter-individual variability in CYP3A activity.
conclusionsFollowing the administration of clarithromycin, the onset of hepatic CYP3A inactivation is delayed compared to that of intestinal CYP3A. The time-course of drug-drug interactions due to clarithromycin will vary with the relative contribution of intestinal and hepatic CYP3A to the clearance and bioavailability of a victim substrate.
Indexed as
Identifiers
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.