title: Evaluation of the abuse potential of extended release hydromorphone versus immediate release hydromorphone.
abstract: Immediate release (IR) hydromorphone has experienced significant misuse and abuse. An extended release (ER) hydromorphone formulation has been developed to provide sustained pain relief and may reduce the likelihood for abuse by delaying absorption. In this double-blind, placebo-controlled, randomized, 2-part crossover study, the abuse potential of single oral doses of hydromorphone ER (intact: 16-, 32-, and 64-mg; milled: 8-mg) was compared with 8-mg hydromorphone IR and placebo. After drug administration, subjects with a history of recreational opioid use completed a series of assessments, including subjective effects visual analog scales (eg, drug liking) and Addiction Research Center Inventory With Cole Modification, at several timepoints up to 48 hours postdose. Independent of formulation, maximum at-the-moment drug liking was higher for hydromorphone versus placebo. Maximum drug liking occurred earlier and was higher for 8-mg IR versus 16-mg ER but similar to 32- and 64-mg ER. Most positive effects were lower after 16-mg ER compared with other doses, including 8-mg IR. Bad drug effects were higher for hydromorphone ER, particularly the 64-mg dose. Milled 8-mg ER produced similar subjective effects to 8-mg IR. Comparison of scores after administration of 8-mg IR on 2 separate occasions showed that most assessments exhibited good test-retest reliability, although some scores declined marginally between test and retest. Delayed onset of good drug effects and prominent bad drug effects of hydromorphone ER suggest that, when administered intact, this formulation may have lower abuse potential than hydromorphone IR.
authors.affiliation: Clinical Pharmacology Group, Kendle Early Stage, Toronto, Ontario, Canada.
authors.forename: Megan J
authors.initials: MJ
authors.lastname: Shram
authors.forename: Gayatri
authors.initials: G
authors.lastname: Sathyan
authors.forename: Sarita
authors.initials: S
authors.lastname: Khanna
authors.forename: Iulia Cristina
authors.initials: IC
authors.lastname: Tudor
authors.forename: Rajneesh
authors.initials: R
authors.lastname: Nath
authors.forename: John
authors.initials: J
authors.lastname: Thipphawong
authors.forename: Edward M
authors.initials: EM
authors.lastname: Sellers
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016739:Behavior, Addictive / Q000209:etiology*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004304:Dosage Forms; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D004091:Hydromorphone / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D019966:Substance-Related Disorders / Q000209:etiology*; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D004304:Dosage Forms; D004091:Hydromorphone