Complementary pharmacokinetic measures to further define the profile of once-daily OROS hydromorphone ER during single-dose and steady-state dosing

Conventional measures such as maximum plasma concentration (Cmax) 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% Cmax). 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% Cmax 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.