Single‐dose evaluation of safety, tolerability and pharmacokinetics of newly formulated hydromorphone immediate‐release and hydrophilic matrix extended‐release tablets in healthy Japanese subjects without co‐administration of an opioid antagonist

Abstract

This single dose, open-label study investigated the safety, tolerability and pharmacokinetics of single oral doses of newly formulated immediate-release (IR) and hydrophilic matrix extended-release (ER) hydromorphone tablets in healthy Japanese subjects without co-administration of an opioid antagonist under fasting and fed conditions. Plasma and urinary concentrations of hydromorphone and metabolites were measured by liquid-chromatography tandem mass-spectroscopy. Following administration of the ER tablet, plasma concentrations of hydromorphone slowly increased with a median tmax of 5.0 h and the Cmax decreased to 37% of the IR tablet, while the AUC0-inf was comparable with that of the IR tablet when administered at the same dose. The degree of fluctuation in the plasma concentration for the ER tablet was much lower than that of the IR tablet and certain levels of plasma concentrations were maintained after 24 h of ER dosing. The AUC0-inf and Cmax increased with food for both IR and ER tablets. The AUC0-inf of hydromorphone-3-glucoside was one-tenth of that of hydromorphone-3-glucuronide. A single oral administration of the hydromorphone tablets would be well-tolerated in healthy Japanese subjects despite a lack of co-administration of an opioid antagonist and the newly developed ER hydromorphone tablets may have the appropriate PK characteristics for once-daily dosing.

Hydromorphone and codeine concentrations in oral fluid specimens from patients receiving substitution therapy with Substitol™ (morphine sulfate)

“…Therefore, it was of interest to compare OF concentrations resulting from Substitol™ intake with those from patients prescribed hydromorphone. A pharmacokinetic study of single-dose hydromorphone showed maximal plasma concentrations in a very low ng/ml range, 24 in agreement with our results for OF concentrations in patients treated for pain with hydromorphone. The OF/serum ratio for hydromorphone has not been previously reported, and was found to be close to 1.…”

Identification of Circulating miRNAs Differentially Regulated by Opioid Treatment

“…The primary objective of the study was to evaluate the safety, tolerability, and pharmacokinetics profiles following single doses of immediate-release and extended release (ER) hydromorphone tablets in healthy male Japanese subjects [19]. For miRNA measurement, blood samples were collected from a treatment group comprising six individuals administered with 6 mg of ER tablets of hydromorphone (Daiichi Sankyo Co., Ltd., Tokyo, Japan).…”

“…Measurements were performed on blood samples previously collected from two independent clinical studies, in which extended-release (ER) tablets of hydromorphone or oxycodone were administered to healthy male volunteers [19,20]. …”

Pharmacokinetic Bioequivalence Studies of an Extended-Release Oxycodone Hydrochloride Tablet in Healthy Japanese Subjects Under Fasting and Fed Conditions Without an Opioid Antagonist

“…Hydrophilic matrix technology is a method for ER of drugs and has been widely used for oral controlled delivery of various drugs, including hydromorphone [10]. Given their hydrophilic nature, these polymers begin to swell upon contact with water, forming a gel layer.…”