Clearance of Hydromorphone ER is Predictable and Stable Over Time

LAS VEGAS, NV — John Thipphawong, MD, from Janssen Pharmaceuticals, Fremont, CA, and colleagues reported at PAINWeek 2012 that the clearance of OROS hydromorphone extended-release (ER) is predictable, stable over time, and not markedly impacted by most demographic characteristics in patients with chronic osteoarthritis pain.

This clinical trial examined the population pharmacokinetics of hydromorphone ER in 407 patients with chronic osteoarthritis pain in a 12-week, fixed dose (8mg [n=212] and 16mg [n=195]) clinical trial. Steady-state plasma samples were taken from each patient on three occasions (Weeks 1, 3, and 6). The covariates tested were sex, race, age, weight, height, body mass index, target joint, sedative use, prior opioid use, and radiographic index. The trial sought to develop a population pharmacokinetic model to explore the impacts of demographic and patient characteristic data on steady-state clearance (CL/F).

The mean plasma concentrations of OROS hydromorphone ER at Weeks 1, 3, and 6 were approximately dose-proportional for 16mg (1.55ng/mL, 1.56ng/mL, and 1.45ng/mL) and for 8mg (0.78ng/mL, 0.82ng/mL, and 0.85ng/mL). The steady-state clearance had a typical value of 484L/h. Both body weight and age were significant covariates (P<0.001), which suggests their potential impact on steady-state clearance. Based on the median age of 58.5 years, steady-state clearance is predicted to be increased by 5% for every 10kg increase in weight. Based on the median weight of 98kg, steady-state clearance is predicted to be decreased by 9% by each decade increase in age.

The researchers concluded that the findings are consistent with healthy volunteer data. Study results indicate that OSOS hydromorphone ER clearance is predictable, stable over time, and not markedly impacted by most demographic characteristics.