title: A randomized study of the effects of food on the pharmacokinetics of once-daily extended-release hydromorphone in healthy volunteers.
abstract: This randomized, open-label, crossover study investigated the influence of food on the pharmacokinetics of extended-release hydromorphone in 30 healthy volunteers. Participants received extended-release hydromorphone 16 mg in the fasted state and immediately after a high-fat breakfast. In addition, the pharmacokinetics of a 16-mg dose of extended-release hydromorphone and a 16-mg daily dose (4 mg qid) of immediate-release hydromorphone in the fasted state were compared. Treatments were separated by washout periods of 7 to 14 days. Naltrexone was given throughout each treatment period to block the opioid effects of hydromorphone. The 90% confidence intervals (CIs) of the ratios of geometric means for maximum plasma concentrations (C(max)) and area under the plasma concentration-time curve (AUC) for extended-release hydromorphone in the fed and fasted states were within the bioequivalence criteria range of 80% to 125%. In the fasted state, the 90% CIs of the ratios of AUC geometric means for extended-release hydromorphone and immediate-release hydromorphone were also within the bioequivalence range. Both hydromorphone treatments were well tolerated. This study shows that the bioavailability of extended-release hydromorphone is not affected by food and that the bioavailability of extended-release hydromorphone under fasting conditions is comparable with that of the immediate-release formulation when administered at the same total daily dose.
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development, 1125 Trenton-Harbourton Rd, Titusville, NJ 08560, USA. tmoore17@its.jnj.com
authors.forename: Kenneth Todd
authors.initials: KT
authors.lastname: Moore
authors.forename: Dominique
authors.initials: D
authors.lastname: St-Fleur
authors.forename: Nadia Cardillo
authors.initials: NC
authors.lastname: Marricco
authors.forename: Jay
authors.initials: J
authors.lastname: Ariyawansa
authors.forename: Véronique
authors.initials: V
authors.lastname: Pagé
authors.forename: Jayalakshmi
authors.initials: J
authors.lastname: Natarajan
authors.forename: Gaetano
authors.initials: G
authors.lastname: Morelli
authors.forename: Ute
authors.initials: U
authors.lastname: Richarz
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016001:Confidence Intervals; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D059305:Diet, High-Fat; D005215:Fasting; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D004091:Hydromorphone / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D009271:Naltrexone / Q000008:administration & dosage; D013810:Therapeutic Equivalency
chemical_list: D003692:Delayed-Action Preparations; D009271:Naltrexone; D004091:Hydromorphone