Open Access(205) Steady‐State Pharmacokinetic Comparison of Morphelan® ROER® (Morphine Sulfate Rapid Onset Extended Release) Once‐a‐Day and Morphine Oral Solution Administered Q4H around‐the‐Clock in Healthy Volunteers
Author(s) -
Eliot Lise,
Loewen Gordon,
Butler Jackie,
Tembe Estella
Publication year - 2001
Publication title -
pain medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.893
H-Index - 97
eISSN - 1526-4637
pISSN - 1526-2375
DOI - 10.1046/j.1526-4637.2001.01039-6.x
Subject(s) - morphine , dosing , pharmacokinetics , medicine , cmax , anesthesia , pharmacology , trough concentration , pharmacodynamics
Controlled‐release morphine formulations have been developed to decrease the dosing frequency needed to maintain pain control around‐the‐clock (ATC). Morphelan® ROER® (MROER), a novel, once‐a‐day, rapid onset extended release morphine formulation, was designed to rapidly reach target concentrations and to maintain therapeutic concentrations throughout a 24‐hour dosing interval. Objective: To compare 24‐hour steady‐state pharmacokinetic profiles of morphine following MROER once‐daily and morphine oral solution (MOS) administered q4h ATC. Methods: In an open‐label, cross‐over study, 12 healthy volunteers were randomized to MROER 60 mg once‐daily or 10 mg q4h ATC MOS for 5 days with at least a 7‐day washout before cross‐over. Twenty‐four‐hour pharmacokinetic profiles were obtained on the last day of each study treatment. Results: Once‐daily MROER rapidly releases morphine, providing plasma morphine concentrations at 30 minutes (C30min) similar to MOS following administration. Maximum concentrations (Cmax), total systemic exposure (AUC0‐24h), peak‐to‐trough fluctuations (%FI) and plasma concentrations at 24 h (C24h) were similar between MROER once‐a‐day and MOS dosed q4h ATC over a 24 hour dosing interval (Table 1). Data are presented as mean ± SD. No statistical differences were observed (p < 0.05). # FL: Number of daily peak‐to‐trough fluctuations. Conclusions: MROER once‐a‐day rapidly reaches target plasma morphine concentrations and maintains similar therapeutic concentrations as MOS dosed q4h ATC over a 24‐hour dosing interval with fewer peak‐to‐trough fluctuations. Therefore, MROER represents a true once‐a‐day controlled‐release morphine formulation. 1Parameter MROER (once‐a‐day) MOS (q4h ATC)AUC0‐24h (ng×h /ml) 273 ± 81.2 279 ± 63.0 Cmax (ng/ml) 18.7 ± 7.13 20.0 ± 4.82 C30min (ng/ml) 12.9 ± 6.64 15.0 ± 4.05 C24h (ng/ml) 7.84 ± 2.99 9.45 ± 2.81 %FI 106 ± 78.1 116 ± 26.7 # FL 1 6