ArticleBritish journal of clinical pharmacology2025
Evaluation of the effect of CYP2D6 and OCT1 polymorphisms on the pharmacokinetics of tramadol: Implications for clinical safety and dose rationale in paediatric chronic pain.
Article in British journal of clinical pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Tramadol-Induced Persistent Singultus: A Case Report on Diagnosis, Mechanism, and Management.Clinical case reports · 2026Article
- Impact of CYP Enzyme Polymorphisms on Opioid Response in Anesthesia and Pain Medicine.Pain research & management · 2026Review
- Evaluation of the effect of CYP2D6 and OCT1 polymorphisms on the pharmacokinetics of tramadol: Implications for clinical safety and dose rationale in paediatric chronic pain.British journal of clinical pharmacology · 2025Article
- Use of lorazepam for analgosedation during mechanical ventilation in pediatric intensive care.Frontiers in medicine · 2025Article
- Empagliflozin in paediatric heart failure: model-based optimisation of a pharmacokinetic bridging study.Frontiers in medicine · 2025Article
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Authors and funding
3 authors.
Funding
Abstract
aimsOur investigation aimed to assess the dose rationale of tramadol in paediatric patients considering the effect of CYP2D6/OCT1 polymorphisms on systemic exposure. Recommendations were made for the oral dose of tramadol to be used in a prospective study in children (3 months to < 18 years old) with chronic pain.
methodsIntravenous pharmacokinetic and genotype data from neonatal patients (n = 46) were available for this analysis. The time course of tramadol and O-desmethyltramadol (M1) concentrations was characterized using a nonlinear mixed effects approach in conjunction with extrapolation principles. Clinical trial simulations were then implemented to explore the effects of polymorphism, maturation and developmental growth on the disposition of tramadol and M1. Reported efficacious exposure range in adult subjects were used as reference.
resultsThe pharmacokinetics of tramadol and M1 was characterized by a two-compartment model. The total clearance of tramadol (CLPP) comprised CYP2D6-mediated metabolism (CLPM) and other pathways (CLPO). Age-related changes in CLPM, CLPO and M1 clearance (CLMO) were described by a sigmoid function, with CYP2D6 as a covariate on CLPP and CLPM, and OCT1 on CLMO. Simulation scenarios including different CYP2D6/OCT1 combinations revealed that steady-state concentrations are above the putative ranges for analgesia in >15% and >70% of subjects after doses of 3 and 8 mg/kg, respectively.
conclusionsIn the absence of genotyping, reference exposure ranges can be used to define the dose rationale for tramadol in paediatric chronic pain. However, a starting dose of 0.5 mg/kg/day should be considered, followed by stepwise titration to the desired analgesic response.
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