title: Complementary pharmacokinetic measures to further define the profile of once-daily OROS hydromorphone ER during single-dose and steady-state dosing.
abstract: Conventional measures such as maximum plasma concentration (C max ) and area under the concentration versus time curve (AUC) may be insufficient to fully describe the pharmacokinetic (PK) profile of extended-release (ER) formulations. A complementary measure, the half-value duration (HVD), corresponds to the period of time during a dosing cycle that plasma concentration is at or above half the value of the maximal concentration (i.e. ≥50% C max ). The current post-hoc analysis uses data from 2 previously published studies comparing the PK profiles and HVD of OROS hydromorphone ER (16 mg administered once daily) and immediate-release (IR) hydromorphone (4 mg administered every 6 hours), calculating single-dose and steady-state condition values. Bioequivalence was demonstrated between the 2 formulations. Mean steady-state once-daily OROS hydromorphone ER concentrations were elevated for most of the 24-hour dosing period and for significantly longer than with the dose-equivalent IR hydromorphone regimen. The duration of time spent ≥50% C max was, on average, 2.7 times longer at steady state for the ER formulation, which also maintained steady-state hydromorphone plasma concentrations, with 65% lower mean degree of fluctuation versus IR hydromorphone. Both formulations appeared to be well tolerated.
authors.affiliation: Clinical Pharmacology & Pharmacokinetics, Mallinckrodt Inc., 325 James McDonnell Blvd 302W-3, Hazelwood, MO 63042 USA.
authors.forename: Krishna
authors.initials: K
authors.lastname: Devarakonda
authors.affiliation: Clinical Pharmacology, Janssen Research & Development, Beerse, Belgium.
authors.forename: Joris
authors.initials: J
authors.lastname: Vandenbossche
authors.affiliation: Global Medical Affairs Lead, Janssen Global Services, Zug, Switzerland.
authors.forename: Ute
authors.initials: U
authors.lastname: Richarz
keywords: Chronic pain; Extended-release; Hydromorphone; Opioids; Pharmacokinetics