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Steady-state pharmacokinetics of extended-release hydromorphone (OROS® hydromorphone): A randomized study in healthy volunteers

Kenneth Todd Moore, MSc, Dominique St-Fleur, BSc, Nadia Cardillo Marricco, MSc, Jay Ariyawansa, MSc, Véronique Pagé, MSc, Jayalakshmi Natarajan, PhD, Gaetano Morelli, MD, FRCP, Ute Richarz, MD

Abstract


The steady-state pharmacokinetics of an extended-release formulation of hydromorphone, OROS® hydromorphone, was investigated in a randomized, openlabel, crossover study in healthy volunteers. Participants were randomly assigned to receive 16 mg of OROS hydromorphone once daily and 4 mg of immediaterelease hydromorphone four times daily for five consecutive days. The two treatments were separated by a washout period of 7-14 days. Naltrexone was given throughout both treatment periods to block the opioid effects of hydromorphone. Steady-state hydromorphone concentrations were statistically analyzed using Helmert contrasts to determine when steady state was reached. A total of 30 participants were enrolled, of whom 29 completed both treatment periods. The two treatments produced comparable steady-state plasma drug concentrations, but peakto-trough fluctuations were smaller with OROS hydromorphone (61 percent vs 172 percent) in comparison with immediate release hydromorphone. Overall systemic exposure to hydromorphone was similar between the two formulations. The ratio of the geometric means between the two formulations for the area under the concentration-time curves at steady state was 105.2 percent with a 90% confidence interval (CI) of 99.8-110.8 (geometric mean: 102.7 percent; 90% CI: 97.6-108.2 after correcting for measured drug content), which was within the bioequivalence range (80-125 percent). The analysis of Helmert contrasts showed that steadystate conditions were attained by day 4. Both treatments were well tolerated. This study shows that OROS hydromorphone maintains steady-state plasma drug concentrations within the same range as immediate-release hydromorphone at the same total daily dose, with less fluctuation.

Keywords


OROS hydromorphone, extended-release hydromorhphone, pharmacokinetics, opioids, osmotic pump

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References


Quigley C: Hydromorphone for acute and chronic pain. Cochrane Database Syst Rev. 2002; 1: CD003447.

Hill HF, Coda BA, Tanaka A, et al.: Multiple-dose evaluation of intravenous hydromorphone pharmacokinetics in normal human subjects. Anesth Analg. 1991; 72: 330-336.

McCarberg BH, Barkin RL: Long-acting opioids for chronic pain: Pharmacotherapeutic opportunities to enhance compliance, quality of life, and analgesia. Am J Ther. 2001; 8: 181-186.

Gupta S, Sathyan G: Providing constant analgesia with OROS hydromorphone. J Pain Symptom Manage. 2007; 33 (Suppl 2S): S19-S24.

Conley R, Gupta SK, Sathyan G: Clinical spectrum of the osmotic-controlled release oral delivery system (OROS), an advanced oral delivery form. Curr Med Res Opin. 2006; 22: 1879-1892.

Drover DR, Angst MS, Valle M, et al.: Input characteristics and bioavailability after administration of immediate and a new extended-release formulation of hydromorphone in healthy volunteers. Anesthesiology. 2002; 97: 827-836.

Sathyan G, Xu E, Thipphawong J, et al.: Pharmacokinetic investigation of dose proportionality with a 24-hour controlled-release formulation of hydromorphone. BMC Clin Pharmacol. 2007; 7: 3.

Sathyan G, Xu E, Thipphawong J, et al.: Pharmacokinetic profile of a 24-hour controlled-release OROS® formulation of hydromorphone in the presence and absence of food. BMC Clin Pharmacol. 2007; 7: 2.

Sathyan G, Sivakumar K, Thipphawong J: Pharmacokinetic profile of a 24-hour controlled-release OROS formulation of hydromorphone in the presence of alcohol. Curr Med Res Opin. 2008; 24: 297-305.

Angst MS, Drover DR, Lötsch J, et al.: Pharmacodynamics of orally administered sustained-release hydromorphone in humans. Anesthesiology. 2001; 94: 63-73.

Palangio M, Northfelt DW, Portenoy RK, et al.: Dose conversion and titration with a novel, once-daily, OROS osmotic technology, extended-release hydromorphone formulation in the treatment of chronic malignant or nonmalignant pain. J Pain Symptom Manage. 2002; 23: 355-368.

Wallace M, Skowronski R, Khanna S, et al.: Efficacy and safety evaluation of once-daily OROS hydromorphone in patients with chronic low back pain: A pilot open-label study (DO-127). Curr Med Res Opin. 2007; 23: 981-989.

Wallace M, Rauck RL, Moulin D, et al.: Once-daily OROS hydromorphone for the management of chronic nonmalignant pain: A dose-conversion and titration study. Int J Clin Pract. 2007; 61: 1671-1676.

Hale M, Tudor IC, Khanna S, et al.: Efficacy and tolerability of once-daily OROS hydromorphone and twice-daily extended-release oxycodone in patients with chronic, moderate to severe osteoarthritis pain: Results of a 6-week, randomized, open-label, noninferiority analysis. Clin Ther. 2007; 29: 874-888.

Hanna M, Thipphawong J; the 118 Study Group: A randomized, double-blind comparison of OROS® hydromorphone and controlled-release morphine for the control of chronic cancer pain. BMC Palliat Care. 2008; 7: 17.

Hanna M, Tuca A, Thipphawong J: An open-label, 1-year extension study of the long-term safety and efficacy of once-daily OROS® hydromorphone in patients with chronic cancer pain. BMC Palliat Care. 2009; 8: 14.

Wallace M, Moulin DE, Rauck RL, et al.: Long-term safety, tolerability, and efficacy of OROS hydromorphone in patients with chronic pain. J Opioid Manag. 2009; 5: 97-105.

Chow SC, Liu JP: Design and Analysis of Bioavailability and Bioequivalence Studies. New York: Marcel Dekker, 1992.

Burnham KP, Anderson DR: Model Selection and Multimodal Inference: A Practical Information-Theoretic Approach. 2nd ed. New York: Springer Science+Media, Inc., 2002.

Hays H, Hagen N, Thirlwell M, et al.: Comparative clinical efficacy and safety of immediate release and controlled release hydromorphone for chronic severe cancer pain. Cancer. 1994; 74: 1808-1816.

Bruera E, Sloan P, Mount B, et al.: A randomized, double-blind, double-dummy, crossover trial comparing the safety and efficacy of oral sustained-release hydromorphone with immediate-release hydromorphone in patients with cancer pain. Canadian Palliative Care Clinical Trials Group. J Clin Oncol. 1996; 14: 1713-1717.




DOI: https://doi.org/10.5055/jom.2010.0032

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