ASSESSMENT OF CYP2D6*10 POLYMORPHISM WITH POST HERPETIC NEURALGIA PATIENTS UNDERGOING TRAMADOL TREATMENT

Authors

  • Namita Vilas Nasare Department of Pharmacology, University College of Medical Sciences & G. T. B. Hospital, Delhi 110095, Environmental Biochemistry and Molecular Biology Laboratory, Department of Biochemistry, University College of Medical Sciences & G. T. B. Hospital, Delhi 110095
  • Pramod Kumari Mediratta Department of Pharmacology, University College of Medical Sciences & G. T. B. Hospital, Delhi 110095
  • Basu Dev Banerjee Environmental Biochemistry and Molecular Biology Laboratory, Department of Biochemistry, University College of Medical Sciences & G. T. B. Hospital, Delhi 110095
  • Pravin Suryakantrao Deshmukh Environmental Biochemistry and Molecular Biology Laboratory, Department of Biochemistry, University College of Medical Sciences & G. T. B. Hospital, Delhi 110095
  • Ashok Kumar Saxena Department of Anesthesia, University College of Medical Sciences & G. T. B. Hospital, Delhi 110095
  • Sambit Nath Bhattacharya Department of Dermatology and Venerology, University College of Medical Sciences (University of Delhi) and GTB Hospital, Dilshad Garden, New Delhi 110095
  • Rafat S. Ahmed Environmental Biochemistry and Molecular Biology Laboratory, Department of Biochemistry, University College of Medical Sciences & G. T. B. Hospital, Delhi 110095

Keywords:

Post Herpetic Neuralgia, CYP2D6*10 allele, Tramadol, PCR- RFLP, Clinical trial

Abstract

objective: To evaluate association of CYP2D6*10 polymorphism with respect to demographic characteristics (age at onset, genders and weight), numerical rating scale (NRS) for measuring pain intensity in relation with resting and movement associated pain and adverse drug effects of PHN patients receiving tramadol therapy.

Methods: Total 246 patients of PHN (148 males and 98 females) were selected who fulfilled the inclusion/exclusion criteria. Clinicians were recorded numerical rating scores (at rest and with movement), and note down adverse drug side effects during the time of study. All samples were analyzed for CYP2D6*10 polymorphism using PCR-RFLP method.

results: We observed genotype distribution of CYP2D6* 10 did not vary significantly with age at onset [non-responders (p=0.317) and responders (p=0.260)], genders[ non-responders (p=0.317) and responders (p=0.949)], and weight [non-responders (p=0.298) and responders (p=0.279)] and also did not find significant role with respect to resting (p=0.428) and movement associated type of pain (p=0.178). In addition, CYP2D6*10 was not associated with adverse effects such as somnolence (p=0.135), dizziness (p=0.178), local site reactions (p=0.535), headache (p=0.502), hypotension (p=0.567) and nausea and vomiting (p=0.268) of analgesic therapy. Therefore we conclude that, CYP2D6*10 may not be a predictor of treatment outcomes of patients with PHN receiving tramadol.

Downloads

Download data is not yet available.

References

Boureau F, Legallicier P, Kabir-Ahmadi M. Tramadol in post-herpetic neuralgia: a randomized, double-blind, placebo-controlled trial. Pain 2003;104:323-31.

Saxena AK, Nasare N, Jain S, Dhakate G, Ahmed RS, Bhattacharya SN, et al. A randomized, prospective study of efficacy and safety of oral tramadol in the management of post-herpetic neuralgia in patients from north India. Pain Pract 2013;13:264-75.

Nasare NV, Deshmukh PS, Banerjee BD, Mediratta PK, Ahmed RS, Saxena AK, et al. CYP2D6*4 polymorphism in tramadol treatment and its clinical impact in patients of post herpetic neuralgia. Pers Med 2012;9:371–85.

Nasare NV, Banerjee BD, Deshmukh SP, Mediratta PK, Saxena AK, Ahmed RS, et al. CYP2D6*2 polymorphism as a predictor of failed outpatient tramadol therapy in postherpetic neuralgia patients. Am J Ther 2013;5. [Epub ahead of print] Pub Med PMID: 23567787

Harati Y, Gooch C, Swenson M, Edelman S, Greene D, Raskin P, et al. Double-blind randomized trial of tramadol for the treatment of the pain of diabetic neuropathy. Neurol 1998;50:1842-6.

Hollingshead J, Dühmke RM, Cornblath DR. Tramadol for neuropathic pain. Cochrane Database Syst Rev 2006;19:CD003726.

Sindrup SH, Andersen G, Madsen C, Smith T, Brosen K, Jensen TS. Tramadol relieves pain and allodynia in polineuropathy: a randomised, double-blind, controlled trial. Pain 1999;83:85-90.

Follin SL, Charland SL. Acute pain management: operative or medical procedures and trauma. Ann Pharmacother 1997;31:1068-76.

Gan SH, Ismail R, Wan Adnan, WA Zulmi W. Impact of CYP2D6 genetic polymorphism on tramadol pharmacokinetics and pharmacodynamics. Mol Diagn Ther 2007;11:171-81.

Stamer U, Stuber F, Muders T, Musshoff F. Respiratory depression with tramadol in a patient with renal impairment and CYP2D6 gene duplication. Anesth Analg 2008;107:926–9.

Rendic S. Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev 2002;34:383-448.

Ingelman-Sundberg M. Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity. Pharmacogenomics J 2005;5:6–13.

Poulsen L, Arendt NL, Brosen K, Sindrup SH. The hypoalgesic effect of tramadol in relation to CYP2D6. Clin Pharmacol Ther 1996;60:636-44.

Stamer UM, Musshoff F, Kobilay M, Madea B, Hoeft A, Stuber F. Concentrations of tramadol and O-desmethyltramadol enantiomers in different CYP2D6 genotypes. Clin Pharmacol Ther 2007;82:41-7.

Stamer UM, Lehnen K, Hothker F, Bayerer B, Wolf S, Hoeft A, et al. Impact of CYP2D6 genotype on postoperative tramadol analgesia. Pain 2003;105:231-8.

Candiotti KA, Yang Z, Rodriguez Y, Crescimone A, Sanchez GC, Takacs P, et al. The impact of CYP2D6 genetic polymorphisms onpostoperative morphine consumption. Pain Med 2009;10:799-805.

Yang Z, Arheart KL, Morris R, Zhang Y, Rodriguez Y, Song C, et al. CYP2D6 poor metabolizer genotype and smoking predict severepostoperative pain in female patients on arrival to the recovery room. Pain Med 2012;13:604-9.

Sindrup SH, Poulsen L, Brosen K, Nielsen A, Gram LF. Are poor metabolisers of sparteine/debrisoquine less pain tolerant than extensive metabolisers? Pain 1993;53:335-9.

Ismail R, Teh LK. Genetic polymorphism of CYP2D6: malaysian Indians have the highest frequency for CYP2D6*4 in Asia. Eur J Clin Pharmacol 2001;57:617-8.

Ismail R. CYP2D6 genotype and phenotype relationship in South Indians. J Postgrad Med 2006;52:245.

Bradford LD. CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants. Pharmacogenomics 2002;3:229-43.

Sachse C, Brockmoller J, Bauer S. Roots I. Cytochrome P450 2D6 variants in a Caucasian population: allele frequencies and phenotypic consequences. Am J Hum Genet 1997;60:284-95.

Ji L, Pan S, Marti-Jaun J, Hanseler E, Rentsch K, Hersberger M. Single-step assays to analyze CYP2D6 gene polymorphisms in Asians: allele frequencies and a novel *14B allele in mainland Chinese. Clin Chem 2002;48:983-8.

Naveen AT, Prasanna T, Farzana BL, Rajan S, Adithan C. CYP2D6 genotype and phenotype relationship in South Indians. J Post Grad Med 2006;52:253-6.

Hartrick CT, Kovan JP, Shapiro S. The numeric rating scale for clinical pain measurement: a ratio measure? Pain Pract 2003;3:310–6.

Nageswararao D, Manjula G, Sailaja K, Raghunadharao S, Andvishnupriya R. Association of CYP2D6*4 polymorphism with acute leukemia. J Cell Tissue Res 2010;10:2201–5.

Kirchheiner J, Keulen J-T HA, Bauer S, Roots I, Brockmöller J. Effects of the CYP2D6 gene duplication on the pharmacokinetics and pharmacodynamics of tramadol. J Clin Psychopharmacol 2008;28:78–83.

Wang G, Zhang H, He F, Fang X. Effect of the CYP2D6 * 10 C188T polymorphism on postoperative tramadol analgesia in a Chinese population. Eur J Clin Pharmacol 2006;62:927–31.

Dworkin RH, Schmader KE, Watson CPN, Gershon AA. The epidemiology and natural history of herpes zoster and post herpetic neuralgia. Elsevier Press NY USA 2001;2:39–64.

Volpi A, Gatti A, Pica F, Bellino S, Marsella LT, Sabato AF. Clinical and psychosocial correlates of acute pain in herpes zoster. J Med Virol 2007;38:275–9.

Meister W, Neiss A, Gross G, Doerr HW, Hobel W, Malin JP, et al. A prognostic score for postherpetic neuralgia in ambulatory patients. Infection 1998;26:359–63.

Jung BF, Johnson RW, Griffin DR, Dworkin RH. Risk factors for postherpetic neuralgia in patients with herpes zoster. Neurol 2004;62:1545–51.

Volpi A, Gatti A, Pica F, Bellino S, Marsella LT, Sabato AF. Clinical and psychosocial correlates of post-herpetic neuralgia. J Med Virol 2008;80:1646–52.

Parruti G, Tontodonati M, Rebuzz C, Polilli E, Sozio F, Consorte A, et al. Predictors of pain intensity and persistence in a prospective Italian cohort of patients with herpes zoster: relevance of smoking, trauma and antiviral therapy. BMC Med 2010;8:58.

Coen PG, Scott F, Leedham Green M, Nia T, Jamil A, Johnson RW, et al. Predicting and preventing post-herpetic neuralgia: are current risk factors useful in clinical practice? Eur J Pain 2006;10:695–700.

Gauthier A, Breuer J, Carrington D, Martin M, Rémy V. Epidemiology and cost of herpes zoster and post-herpetic neuralgia in the United Kingdom. Epidemiol Infect 2008;9:1–10.

Gauthier A, Breuer J, Carrington D, Martin M, Remy V. Epidemiology and cost of herpes zoster and post-herpetic neuralgia in the United Kingdom. Epidemiol Infect 2009;137:38-47.

Chidiac C, Brucelle J, Daures JP, Hoang-Xuan T, Morel P, Leplege A, et al. Characteristics of patients with herpes zoster on presentation to practitioners in France. Clin Infect Dis 2001;33:62–9.

Fleming DM, Cross KW, Cobb WA, Chapman RS. Gender difference in the incidence of shingles. Epidemiol Infect 2004;132:1–5.

Opstelten W, Van Essen GA, Schellevis F, Verheij TJ, Moons KG. Gender as an independent risk factor for herpes zoster: a population-based prospective study. Ann Epidemiol 2006;16:692–5.

Schmader K, Gorge LK, Burchett BM, Pieper CF, Hamilton JD. Racial differences in the occurrence of herpes zoster. J Infect Dis 1995;171:701–4.

Concato J, Peduzzi P, Holford TR, Feinstein AR. Importance of events per independent variable in proportional hazards analysis. I. Background, goals, and general strategy. J Clin Epidemiol 1995;48:1495–501.

Choo PW, Galil K, Donahue JG, Walker AM, Spiegelman D, Platt R. Risk factors for postherpetic neuralgia. Arch Intern Med 1997;57:1217–24.

Decroix J, Partsch H, Gonzales R, Mobacken H, Goh CL, Walsh L, et al. Factors influencing pain outcome in herpes zoster: an observational study with valaciclovir. Valaciclovir International Zoster Assessment Group (VIZA). J Eur Acad Dermatol Venereol 2000;14:23–33.

Dworkin RH, Cooper EM, Siegfried RN. Chronic pain and disease conviction. Clin J Pain 1996;12:111-7.

Scott FT, Leedham-Green ME, Barrett-Muir WY, Hawrami K, Gallagher WJ, Johnson R, et al. A study of shingles and the development of postherpetic neuralgia in east London. J Med Virol 2003;70:S24–S30.

Drolet M, Brisson M, Schmader KE, Levin M, Johnson R, Oxman M, et al. The impact of herpes zoster and postherpetic neuralgia on health-related quality of life: a prospective study. CMAJ 2010;182:1731–6.

Anderson GD. Gender differences in pharmacological response. Int Rev Neurobiol 2008;83:1–10.

Soldin OP, Mattison DR. Sex differences in pharmacokinetics and pharmacodynamics. Clin Pharmacokinet 2009;48:143–57.

Schwartz JB. The current state of knowledge on age, sex, and their interactions on clinical pharmacology. Clin Pharmacol Ther 2007;82:87–96.

Scandlyn MJ, Stuart EC, Rosengren RJ. Sex-specific differences in CYP450 isoforms in humans. Expert Opin Drug Metab Toxicol 2008;4:413–24.

Bergman U, Wiholm BE. Patient medication on admission to a medical clinic. Eur J Clin Pharmacol 1981;20:185–91.

Veehof LJG, Stewart RE, Meyboom-de Jong B, Haaijer-Ruskamp FM. Adverse drug reactions and polypharmacy in the elderly in general practice. Eur J Clin Pharmacol 1999;55:533–6.

Fattinger K, Roos M, Vergères P, Holenstein C, Kind B, Masche U, et al. Epidemiology of drug exposure and adverse drug reactions in two swiss departments of internal medicine. Br J Clin Pharmacol 2000;49:158-67.

Jensen MP, Chen C, Brugger AM. Post surgical pain outcome assessment. Pain 2002;99:101–9.

McCarthy M Jr, Chang CH, Pickard AS, Giobbie-Hurder A, Price DD, et al. Visual analog scales for assessing surgical pain. J Am Coll Surg 2005;201:245–52.

Li Q, Wang R, Guo Y, Wen S, Xu L, Wang S. Relationship of CYP2D6 genetic polymorphisms and the pharmacokinetics of tramadol in Chinese volunteers. J Clin Pharm Ther 2010;35:239-47.

Slanar O, Dupal P, Matouskova O, Vondrackova H. Tramadol efficacy in patients with postoperative pain in relation to CYP2D6 and MDR1 polymorphisms. Bratisl Lek Listy 2012;113:152-5.

Published

01-11-2014

How to Cite

Nasare, N. V., P. K. Mediratta, B. D. Banerjee, P. S. Deshmukh, A. K. Saxena, S. N. Bhattacharya, and R. S. Ahmed. “ASSESSMENT OF CYP2D6*10 POLYMORPHISM WITH POST HERPETIC NEURALGIA PATIENTS UNDERGOING TRAMADOL TREATMENT”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 6, no. 11, Nov. 2014, pp. 97-102, https://journals.innovareacademics.in/index.php/ijpps/article/view/2963.

Issue

Section

Original Article(s)

Most read articles by the same author(s)