Presented at the 2012 AAPM Annual Meeting « Back

Factors Affecting Urinary Excretion of Amitriptyline in Neuropathic Pain Patients

Sophie J. Bordson, BS, sbordson@ucsd.edu¹, Rabia S. Atayee, PharmD BCPS², Joseph D. Ma, PharmD³, Brookie M. Best, PharmD MAS⁴, Amadeo J. Pesce, PhD DABCC⁵, (1) University of California–San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences, San Diego, California, (2) UCSD Skaggs School of Pharmacy, La Jolla, California, (3) Pharmacy, La Jolla, California, (4) UC San Diego, La Jolla, California, (5) Millennium Research Institute, San Diego, California

Introduction: Amitriptyline is a tricyclic antidepressant used in the treatment of neuropathic pain. It is converted to the active metabolite nortriptyline via CYP2C19, and then nortriptyline is inactivated via CYP2D6. While most drug interaction reports focus on CYP2D6, amitriptyline has more anticholinergic activity than nortriptyline and CYP2C19 interactions may also be important. Methods: This was a retrospective analysis of urinary excretion data obtained from routine monitoring of patients with pain between September 2010 and May 2011. All data were de-identified and the UCSD IRB granted IRB-exempt status. Urine specimens were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) at Millennium Laboratories for the presence of amitriptyline and nortriptyline. Effects of gender, age, urinary pH, CYP2C19 inhibitors, and CYP2D6 inhibitors on the nortriptyline to amitriptyline metabolic ratio (MR) were assessed using Microsoft Excel and Origin Pro 8.5.1. Results: The geometric mean MR was 0.69 in 2015 eligible subjects. Gender, age, and urinary pH had no effect on MR (p > 0.05 for gender; R2 < 0.2 for age and urinary pH). CYP2D6 inhibitors did not significantly affect MR (p = 0.146), and CYP2C19 inhibitors showed a small but significant decrease in MR (p = 0.015). Conclusions: Age, gender, and urinary pH did not affect the MR in subjects taking amitriptyline. Concomitant use of CYP2C19 inhibitors shifted the MR toward relatively higher amitriptyline concentrations; future studies should determine if patients taking CYP2C19 inhibitors experience increased incidence of anticholinergic side effects.

Funding: An unrestricted grant was given to the UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences to fund the summer internships by Millennium Laboratories, Inc.