Abstract

TRANSLATIONAL MEDICINE: IMPACT ON CYP2D6 POLYMORPHISM WITH RESPECT TO TRAMADOL TREATMENT IN POST HERPETIC NEURALGIA PATIENTS

Namita Vilas Nasare M. Pharm, PhD*, Pramod Kumari Mediratta MD, Basu Dev Banerjee M. Phil, PhD, Pravin Suryakantrao Deshmukh MSc, PhD, Ashok Kumar Saxena MD, DA, FAMS, Sambit Nath Bhattacharya MD, Rafat S Ahmed MSc, PhD

ABSTRACT

Post Herpetic Neuralgia (PHN) is a chronic neuropathic syndrome. It is more difficult to treat than other types of pain because it does not respond well to normal pain medications. Tramadol is one of the effective drug used in PHN which is metabolized by cytochrome P450 2D6 enzyme. Its activity ranges from complete deficiency to excessive activity, potentially causing toxicity of the medication or therapeutic failure with recommended drug dosages. In this review, we tried represent in a comprehensive way of the published reports including our on clinical, experimental outcome of tramadol with CYP2D6 polymorphism of PHN patients. In these prospective, non responders vs. responders study we mainly focused on the outcome of combinational therapy of tramadol and topical application of 3.33% doxepin with 0.05% capsaicin cream in treating PHN patients. In addition, clinical correlations with CYP2D6 polymorphism with specific reference to the persistence of pain. Clinical-genetical outcome of combinational therapy treatment with tramadol 50 to 200 mg per day was clinically associated with significant pain reduction in terms of enhanced pain relief, reduced sleep interference, greater global improvement, diminished side-effect profile, and improved QOL in PHN patients. In genetic analysis CYP2D6 (*2, *4 and *10) polymorphism may not be a predictors of treatment outcome of patients with PHN receiving tramadol. CYP2D6*4 polymorphism may be as important predictor of experiencing adverse drug reactions Whereas, CYP2D6 (*2 and *10) polymorphisms may not be associated with adverse drug reactions.

Keywords: Pharmacogenetics; CYP2D6; Tramadol; Doxepin; Capsaicin; Clinical trials; Adverse drug reactions; Post Herpetic Neuralgia.