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Assessment of tramadol pharmacokinetics in correlation with CYP2D6 and clinical symptoms.
Drug Metab Pers Ther. 2020 Jun 29 [Online ahead of print]DM

Abstract

Objectives Due to lack of adequate data on tramadol kinetic in relevance of CYP2D6 toxicity, this study was designed to investigate the effect of CYP2D6 phenotype in tramadol poisoning. The saliva, urine and blood samples were taken at the admission time. Consequently, concentration of tramadol and its major metabolites were measured. Methods A pharmacokinetic and metabolic study was developed in cases of tramadol poisoned (n=96). Cases of tramadol poisoned evidenced seizure, hypertension, dizziness, nausea and vomiting symptoms participated. Results Female cases showed higher N-desmethyltramadol (M2) tramadol concentrations than male cases: in urine (40.12 ± 124.53 vs. 7.3 ± 7.13), saliva (16.91 ± 26.03 vs. 5.89 ± 7.02), and blood (1.11 ± 1.56 vs. 0.3 ± 0.38) samples. Significant correlation between blood, saliva, and urine concentrations were found (r = 0.5). Based on the metabolic ratio of O-desmethyltramadol (M1) of male (0.53 ± 0.22) and female (0.43 ± 0.26), poisoning and severe symptoms like seizure in female occurs statistically fewer (13.04%) than in male (50.6%). Assessment of CYP2D6 phenotype showed all of the participants were extensive metabolizers (EM) and their phenotype was associated with clinical symptoms. Conclusions According to our results, M1 as a high potent metabolite has an important role in toxicity and the likelihood of poisoning in people with EM phenotype. Finally, tramadol metabolic ratio may justify the cause of various symptoms in human tramadol poisoning.

Authors+Show Affiliations

Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Food and Drug Vice Presidency, Mashhad University of Medical Sciences, Mashhad, Iran.Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.Biopharmaceutics and Pharmacokinetic Division, Department of Pharmaceutics, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.Department of Clinical Toxicology, Loghman-Hakim Hospital, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Excellent Center of Clinical Toxicology, Ministry of Health and Medical Education, Tehran, Iran.Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32598307

Citation

Ahmadimanesh, Mahnaz, et al. "Assessment of Tramadol Pharmacokinetics in Correlation With CYP2D6 and Clinical Symptoms." Drug Metabolism and Personalized Therapy, 2020.
Ahmadimanesh M, Naeini MB, Rouini MR, et al. Assessment of tramadol pharmacokinetics in correlation with CYP2D6 and clinical symptoms. Drug Metab Pers Ther. 2020.
Ahmadimanesh, M., Naeini, M. B., Rouini, M. R., Shadnia, S., & Ghazi-Khansari, M. (2020). Assessment of tramadol pharmacokinetics in correlation with CYP2D6 and clinical symptoms. Drug Metabolism and Personalized Therapy. https://doi.org/10.1515/dmdi-2019-0021
Ahmadimanesh M, et al. Assessment of Tramadol Pharmacokinetics in Correlation With CYP2D6 and Clinical Symptoms. Drug Metab Pers Ther. 2020 Jun 29; PubMed PMID: 32598307.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Assessment of tramadol pharmacokinetics in correlation with CYP2D6 and clinical symptoms. AU - Ahmadimanesh,Mahnaz, AU - Naeini,Mehri Bemani, AU - Rouini,Mohammad-Reza, AU - Shadnia,Shahin, AU - Ghazi-Khansari,Mahmoud, Y1 - 2020/06/29/ PY - 2019/09/04/received PY - 2020/04/10/accepted PY - 2020/6/30/entrez KW - CYP2D6 KW - concentration KW - metabolites KW - poisoning KW - tramadol JF - Drug metabolism and personalized therapy JO - Drug Metab Pers Ther N2 - Objectives Due to lack of adequate data on tramadol kinetic in relevance of CYP2D6 toxicity, this study was designed to investigate the effect of CYP2D6 phenotype in tramadol poisoning. The saliva, urine and blood samples were taken at the admission time. Consequently, concentration of tramadol and its major metabolites were measured. Methods A pharmacokinetic and metabolic study was developed in cases of tramadol poisoned (n=96). Cases of tramadol poisoned evidenced seizure, hypertension, dizziness, nausea and vomiting symptoms participated. Results Female cases showed higher N-desmethyltramadol (M2) tramadol concentrations than male cases: in urine (40.12 ± 124.53 vs. 7.3 ± 7.13), saliva (16.91 ± 26.03 vs. 5.89 ± 7.02), and blood (1.11 ± 1.56 vs. 0.3 ± 0.38) samples. Significant correlation between blood, saliva, and urine concentrations were found (r = 0.5). Based on the metabolic ratio of O-desmethyltramadol (M1) of male (0.53 ± 0.22) and female (0.43 ± 0.26), poisoning and severe symptoms like seizure in female occurs statistically fewer (13.04%) than in male (50.6%). Assessment of CYP2D6 phenotype showed all of the participants were extensive metabolizers (EM) and their phenotype was associated with clinical symptoms. Conclusions According to our results, M1 as a high potent metabolite has an important role in toxicity and the likelihood of poisoning in people with EM phenotype. Finally, tramadol metabolic ratio may justify the cause of various symptoms in human tramadol poisoning. SN - 2363-8915 UR - https://www.unboundmedicine.com/medline/citation/32598307/Assessment_of_tramadol_pharmacokinetics_in_correlation_with_CYP2D6_and_clinical_symptoms L2 - https://www.degruyter.com/doi/10.1515/dmdi-2019-0021 DB - PRIME DP - Unbound Medicine ER -
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