Unknown

Dataset Information

0

Pharmacokinetic investigation of dose proportionality with a 24-hour controlled-release formulation of hydromorphone.


ABSTRACT: The purpose of this study was investigate the dose proportionality of a novel, once-daily, controlled-release formulation of hydromorphone that utilizes the OROS Push-Pull osmotic pump technology.In an open-label, four-way, crossover study, 32 healthy volunteers were randomized to receive a single dose of OROS hydromorphone 8, 16, 32, and 64 mg, with a 7-day washout period between treatments. Opioid antagonism was provided by three or four doses of naltrexone 50 mg, given at 12-hour intervals pre- and post-OROS hydromorphone dosing. Plasma samples for pharmacokinetic analysis were collected pre-dose and at regular intervals up to 48 hours post-dose (72 hours for the 64-mg dose), and were assayed for hydromorphone concentration to determine peak plasma concentration (Cmax), time at which peak plasma concentration was observed (Tmax), terminal half-life (t1/2), and area under the concentration-time curve for zero to time t (AUC0-t) and zero to infinity (AUC0-infinity). An analysis of variance (ANOVA) model on untransformed and dose-normalized data for AUC0-t, AUC0-infinity, and Cmax was used to establish dose linearity and proportionality.The study was completed by 31 of 32 subjects. Median Tmax (12.0-16.0 hours) and mean t1/2 (10.6-11.0 hours) were found to be independent of dose. Regression analyses of Cmax, AUC0-48, and AUC0-infinity by dose indicated that the relationship was linear (slope, P < or = 0.05) and that the intercept did not differ significantly from zero (P > 0.05). Similar analyses with dose-normalized parameters also indicated that the slope did not differ significantly from zero (P > 0.05).The pharmacokinetics of OROS hydromorphone are linear and dose proportional for the 8, 16, 32, and 64 mg doses.

SUBMITTER: Sathyan G 

PROVIDER: S-EPMC1808051 | biostudies-literature | 2007 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

Pharmacokinetic investigation of dose proportionality with a 24-hour controlled-release formulation of hydromorphone.

Sathyan Gayatri G   Xu Emily E   Thipphawong John J   Gupta Suneel K SK  

BMC clinical pharmacology 20070202


<h4>Background</h4>The purpose of this study was investigate the dose proportionality of a novel, once-daily, controlled-release formulation of hydromorphone that utilizes the OROS Push-Pull osmotic pump technology.<h4>Methods</h4>In an open-label, four-way, crossover study, 32 healthy volunteers were randomized to receive a single dose of OROS hydromorphone 8, 16, 32, and 64 mg, with a 7-day washout period between treatments. Opioid antagonism was provided by three or four doses of naltrexone 5  ...[more]

Similar Datasets

| S-EPMC1810515 | biostudies-literature
| S-EPMC4468955 | biostudies-literature
| S-EPMC5655072 | biostudies-literature
| S-EPMC8453771 | biostudies-literature
| S-EPMC6061088 | biostudies-literature
| S-EPMC6187918 | biostudies-literature
| S-EPMC4562161 | biostudies-literature
| S-EPMC4567387 | biostudies-literature
| S-EPMC3863398 | biostudies-literature
| S-EPMC4510366 | biostudies-literature