ArticleBasic & clinical pharmacology & toxicology2009
Uptake/efflux transport of tramadol enantiomers and O-desmethyl-tramadol: focus on P-glycoprotein.
Article in Basic & clinical pharmacology & toxicology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- The Pharmacogenetics of Tramadol.Clinical pharmacokinetics · 2015Pooled it
- A pharmacokinetic drug-drug interaction study between pregabalin and tramadol in healthy volunteers.European journal of clinical pharmacology · 2018Trial
- Effects of terbinafine and itraconazole on the pharmacokinetics of orally administered tramadol.European journal of clinical pharmacology · 2015Trial
- Rifampicin markedly decreases the exposure to oral and intravenous tramadol.European journal of clinical pharmacology · 2013Trial
- Ticlopidine inhibits both O-demethylation and renal clearance of tramadol, increasing the exposure to it, but itraconazole has no marked effect on the ticlopidine-tramadol interaction.European journal of clinical pharmacology · 2013Trial
- Review of Structural Modification and Development of Novel Tramadol Derivatives.Molecules (Basel, Switzerland) · 2026Review
- The Impact of P-Glycoprotein on Opioid Analgesics: What's the Real Meaning in Pain Management and Palliative Care?International journal of molecular sciences · 2022Review
- Centrally administered CYP2D inhibitors increase oral tramadol analgesia in rats.Brain research bulletin · 2020Article
- Potential Pharmacokinetic Drug-Drug Interactions between Cannabinoids and Drugs Used for Chronic Pain.BioMed research international · 2020Review
- Evaluation of the Effect of CYP2D6 Genotypes on Tramadol andPharmaceutics · 2019Article
- Identification of canine cytochrome P-450s (CYPs) metabolizing the tramadol (+)-M1 and (+)-M2 metabolites to the tramadol (+)-M5 metabolite in dog liver microsomes.Journal of veterinary pharmacology and therapeutics · 2018Article
- Effect ofEvidence-based complementary and alternative medicine : eCAM · 2017Article
- Pharmacokinetics of Tramadol and O-Desmethyltramadol Enantiomers Following Administration of Extended-Release Tablets to Elderly and Young Subjects.Drugs & aging · 2015Article
- Physiologically Based Pharmacokinetic Predictions of Tramadol Exposure Throughout Pediatric Life: an Analysis of the Different Clearance Contributors with Emphasis on CYP2D6 Maturation.The AAPS journal · 2015Article
- Transporter-Mediated Disposition of Opioids: Implications for Clinical Drug Interactions.Pharmaceutical research · 2015Review
- PharmGKB summary: tramadol pathway.Pharmacogenetics and genomics · 2014Article
- Coexistence of passive and proton antiporter-mediated processes in nicotine transport at the mouse blood-brain barrier.The AAPS journal · 2013Article
- Differences between opioids: pharmacological, experimental, clinical and economical perspectives.British journal of clinical pharmacology · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The analgesic effect of tramadol (TMD) results from the monoaminergic effect of its two enantiomers, (+)-TMD and (-)-TMD as well as its opioid metabolite (+)-O-desmethyl-tramadol (M1). P-glycoprotein (P-gp) might be of importance in the analgesic and tolerability profile variability of TMD. Our study investigated the involvement of P-gp in the transepithelial transport of (+)-TMD, (-)-TMD and M1, using a Caco-2 cell monolayer model. The bidirectional transport of racemic TMD and M1 (1-100 microM) across the monolayers was investigated at two pH conditions (pH 6.8/7.4 and 7.4/7.4) in the presence and absence of P-gp inhibitor cyclosporine A (10 microM) and assessed with the more potent and specific P-gp inhibitor GF120918 (4 microM). Analytical quantification was performed by liquid chromatography coupled to the fluorescence detector. A net secretion of (+)-TMD, (-)-TMD and M1 was observed when a pH gradient was applied (TR: P(app)(B - A)/P(app)(A - B): 1.8-2.7; P < 0.05). However, the bidirectional transport of all compounds was equal in the non-gradient system. In the presence of P-gp inhibitors, a slight but significant increase of secretory flux was observed (up to 26%; P < 0.05) at both pH conditions. In conclusion, (+)-TMD, (-)-TMD and M1 are not P-gp substrates. However, proton-based efflux pumps may be involved in limiting the gastrointestinal absorption of TMD enantiomers as well as enhancing TMD enantiomers and M1 renal excretion. A possible involvement of uptake carriers in the transepithelial transport of TMD enantiomers and M1 is suggested.
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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 Socratic graph.