Assessment of tramadol pharmacokinetics in correlation with CYP2D6 and clinical symptoms
Autor: | Shahin Shadnia, Mohammad-Reza Rouini, Mehri Bemani Naeini, Mahnaz Ahmadimanesh, Mahmoud Ghazi-Khansari |
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Rok vydání: | 2020 |
Předmět: |
Adult
Male medicine.medical_specialty Saliva CYP2D6 Adolescent Nausea Metabolite Urine 030226 pharmacology & pharmacy Gastroenterology Young Adult 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics Internal medicine medicine Humans Pharmacology (medical) General Pharmacology Toxicology and Pharmaceutics Tramadol business.industry Middle Aged Analgesics Opioid Kinetics Phenotype Cytochrome P-450 CYP2D6 chemistry 030220 oncology & carcinogenesis Toxicity Female medicine.symptom business medicine.drug |
Zdroj: | Drug Metabolism and Personalized Therapy. |
ISSN: | 2363-8915 2363-8907 |
Popis: | 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. |
Databáze: | OpenAIRE |
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