title: CYP2D6*2 Polymorphism as a Predictor of Failed Outpatient Tramadol Therapy in Postherpetic Neuralgia Patients.
abstract: Human cytochrome P4502D6 (CYP2D6) gene is highly polymorphic, leading to wide interindividual ethnic differences in CYP2D6-mediated drug metabolism. Its activity ranges from complete deficiency to excessive activity, potentially causing toxicity of the medication or therapeutic failure with recommended drug dosages. The aim of the study was to find the association of CYP2D6*2 polymorphisms with demographic characters (age, sex, and weight), pain intensity scales [numerical rating scale (NRS) sleep, global perceived effect (GPE)], and adverse drug effects in postherpetic neuralgia (PHN) patients receiving tramadol. The study comprised 246 patients [including 123 nonresponders (NRs) and 123 responders (Rs)] with PHN undergoing analgesic treatment at the pain clinic, Out Patient Department, University College of Medical Sciences, Guru Teg Bahadur Hospital, Delhi, India. Patients with any history of diabetes mellitus, human immunodeficiency virus, malignancy, hematological or liver disease, psychiatric illness, alcohol abuse, and tramadol sensitivity were excluded from the study. The NRSs of (resting and movement), NRS-sleep, and GPE were evaluated by the treating physician. Adverse drug effects during the time of the study were recorded. All samples were analyzed for CYP2D6*2 polymorphism using the polymerase chain reaction-restriction fragment length polymorphism method. The genotype distribution did not vary significantly among genders [NR (P = 0.723); R (P = 0.947)] and different age groups in NRs (P = 0.763) and Rs (P = 0.268). Clinically, statistically significant (P < 0.001) results were obtained in both the groups when compared with baseline in the NRS-sleep and GPE scores, whereas no association was found between NRS-sleep and GPE scores when compared with CYP2D6*2 genotype (P > 0.05). In addition, CYP2D6*2 genotype was not related to the adverse effects of analgesic therapy. The overall results suggested that CYP2D6*2 polymorphism plays no role in the PHN patients receiving tramadol treatment. The CYP2D6*2 polymorphism may not be a predictor of treatment outcome of patients with respect to PHN-receiving tramadol.
authors.affiliation: 1Department of Pharmacology, University College of Medical Sciences (University of Delhi) and Guru Teg Bahadur Hospital, New Delhi, India; 2Environmental Biochemistry and Molecular Biology Laboratory, Department of Biochemistry, University College of Medical Sciences (University of Delhi) and Guru Teg Bahadur Hospital, New Delhi, India; Departments of3Anesthesia; and 4Dermatology and Venerology, University College of Medical Sciences (University of Delhi) and Guru Teg Bahadur Hospital, New Delhi, India.
authors.forename: Namita Vilas
authors.initials: NV
authors.lastname: Nasare
authors.forename: Basu Dev
authors.initials: BD
authors.lastname: Banerjee
authors.forename: Pravin
authors.initials: P
authors.lastname: Suryakantrao Deshmukh
authors.forename: Pramod Kumari
authors.initials: PK
authors.lastname: Mediratta
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Saxena
authors.forename: Rafat Sultana
authors.initials: RS
authors.lastname: Ahmed
authors.forename: Sambit Nath
authors.initials: SN
authors.lastname: Bhattacharya
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D059645:Mutation Rate; D051474:Neuralgia, Postherpetic / Q000188:drug therapy*; D010045:Outpatients; D010147:Pain Measurement; D012150:Polymorphism, Restriction Fragment Length; D014147:Tramadol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D014147:Tramadol; D019389:Cytochrome P-450 CYP2D6