Trial reportEuropean journal of clinical pharmacology2015
Effects of terbinafine and itraconazole on the pharmacokinetics of orally administered tramadol.
Trial report in European journal of clinical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
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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
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Pooled it
- Effects of Celecoxib and Etoricoxib on the Pharmacokinetics and Pharmacological Effects of Orally Administered Tramadol: A Randomised Controlled Trial.Basic & clinical pharmacology & toxicology · 2026Trial
- Pharmacokinetics of Tramadol and Celecoxib in Japanese and Caucasian Subjects Following Administration of Co-Crystal of Tramadol-Celecoxib (CTC): A Randomised, Open-Label Study.European journal of drug metabolism and pharmacokinetics · 2019Trial
- Pharmacogenomics and Pharmacometabolomics in Precision Tramadol Prescribing for Enhanced Pain Management: Evidence from QBB and EMR Data.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Article
- Influence of cytochromeFrontiers in pharmacology · 2024Article
- Antifungal Selection for the Treatment of Onychomycosis: Patient Considerations and Outcomes.Infection and drug resistance · 2024Review
- Investigation of Drug-Interaction Potential for Arthritis Dietary Supplements: Chondroitin Sulfate, Glucosamine, and Methylsulfonylmethane.Molecules (Basel, Switzerland) · 2023Article
- Design, Synthesis and Biological Evaluation of Lophanic Acid Derivatives as Antifungal and Antibacterial Agents.Molecules (Basel, Switzerland) · 2022Article
- Possible inhibitory effects of terbinafine on aripiprazole metabolism: Two case reports.The mental health clinician · 2021Article
- Evaluation of the Effect of CYP2D6 Genotypes on Tramadol andPharmaceutics · 2019Article
- Population pharmacokinetic analysis of tramadol andDrug design, development and therapy · 2019Article
- Impact of CYP genotype and inflammatory markers on the plasma concentrations of tramadol and its demethylated metabolites and drug tolerability in cancer patients.European journal of clinical pharmacology · 2018Article
- Opioid-induced inhibition of the human 5-HT and noradrenaline transporters in vitro: link to clinical reports of serotonin syndrome.British journal of pharmacology · 2018Article
- Opioid analgesics-related pharmacokinetic drug interactions: from the perspectives of evidence based on randomized controlled trials and clinical risk management.Journal of pain research · 2017Review
- Article
- In Silico Analog Design for Terbinafine Against Trichophyton rubrum: A Preliminary Study.Indian journal of microbiology · 2015Article
- 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
- Potential anti-alopecia constituents fromJournal of advanced pharmaceutical technology & researchArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTramadol is widely used for acute, chronic, and neuropathic pain. Its primary active metabolite is O-desmethyltramadol (M1), which is mainly accountable for the μ-opioid receptor-related analgesic effect. Tramadol is metabolized to M1 mainly by cytochrome P450 (CYP)2D6 enzyme and to other metabolites by CYP3A4 and CYP2B6. We investigated the possible interaction of tramadol with the antifungal agents terbinafine (CYP2D6 inhibitor) and itraconazole (CYP3A4 inhibitor).
methodsWe used a randomized placebo-controlled crossover study design with 12 healthy subjects, of which 8 were extensive and 4 were ultrarapid CYP2D6 metabolizers. On the pretreatment day 4 with terbinafine (250 mg once daily), itraconazole (200 mg once daily) or placebo, subjects were given tramadol 50 mg orally. Plasma concentrations of tramadol and M1 were determined over 48 h and some pharmacodynamic effects over 12 h. Pharmacokinetic variables were calculated using standard non-compartmental methods.
resultsTerbinafine increased the area under plasma concentration-time curve (AUC0-∞) of tramadol by 115 % and decreased the AUC0-∞ of M1 by 64 % (P < 0.001). Terbinafine increased the peak concentration (C max) of tramadol by 53 % (P < 0.001) and decreased the C max of M1 by 79 % (P < 0.001). After terbinafine pretreatment the elimination half-life of tramadol and M1 were increased by 48 and 50 %, respectively (P < 0.001). Terbinafine reduced subjective drug effect of tramadol (P < 0.001). Itraconazole had minor effects on tramadol pharmacokinetics.
conclusionsTerbinafine may reduce the opioid effect of tramadol and increase the risk of its monoaminergic adverse effects. Itraconazole has no meaningful interaction with tramadol in subjects who have functional CYP2D6 enzyme.
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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.