Input Characteristics and Bioavailability after Administration of Immediate and a New Extended-release Formulation of Hydromorphone in Healthy Volunteers

Abstract

The OROS formulation of hydromorphone produced continued release of medication over 24 h, which should allow for once-daily oral dosing. The extended release of hydromorphone will produce less fluctuation of plasma concentrations compared with IR formulations, which should provide for more constant pain control. The in vivo release of hydromorphone from both IR and OROS formulations were adequately described using a linear spline deconvolution approach. The increased bioavailability from the OROS formulation may be related to decreased metabolism by a first-pass effect or enterohepatic recycling of hydromorphone.

The Use of a Sum of Inverse Gaussian Functions to Describe the Absorption Profile of Drugs Exhibiting Complex Absorption

“…The analysis was based on data gathered from two studies in healthy volunteers previously described in (12) and (5).…”

“…The OROS \ formulation is a sustained release system that uses a semipermeable membrane around a drug tablet core which is capable of providing sustained drug release once swallowed orally. Arterial blood samples after administration of the infusion were drawn immediately before the dose and at 1, 3,5,7,10,11,12,13,15,17,20,25,40,55,70,100,130,190,250,370,490,730,970, and 1450 min after drug administration. Venous blood samples after administration of the OROS \ formulations were drawn before the dose and at 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, and 48 h after drug intake.…”

“…The disposition parameters were fixed to the individual empirical Bayesian disposition estimates provided by our previous study, in which a three-compartment model was used to fit the intravenous data (12). The absorption rate was then modeled using a sum of inverse Gaussian functions.…”

“…The disposition parameters were fixed to the individual empirical Bayesian disposition estimates, which were shown to fit the intravenous data adequately with the use of a three-compartment model (12). One and a sum of two and three inverse Gaussian functions were tested as input functions.…”

Use of OROS® hydromorphone in the treatment of osteoarthritis and osteoporosis: A pooled analysis of three non-interventional studies focusing on different starting doses

“…OROS ® hydromorphone (Jurnista®) is a once-daily, extended release hydromorphone formulation, fi rst launched in Germany in 2006. It uses the OROS ® push-pull osmotic technology and consists of an osmotically active bilayer core enclosed in a semi-permeable tablet shell membrane [7], designed to deliver medication at a controlled rate to provide analgesic coverage for 24 hours [8,9]. Th e bioavailability of hydromorphone from OROS ® hydromorphone is minimally aff ected by food [10] and alcohol [11].…”