Effect of Roux-en-Y gastric bypass on the pharmacokinetic-pharmacodynamic relationships of liquid and controlled-release formulations of oxycodone

Louise Ladebo, Ahmad Y Abuhelwa, David J R Foster, Jens P Kroustrup, Grzegorz J Pacyk, Kenneth T Kongstad, Asbjørn M Drewes, Lona L Christrup, Anne E Olesen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

The physiological changes following Roux-en-Y gastric bypass (RYGB) surgery may impact drug release from mechanistically different controlled-release tablets, making generic substitution inappropriate. This study aimed to characterise the pharmacokinetic-pharmacodynamic relationships of oxycodone from a lipid-based and water-swellable controlled-release tablet in RYGB patients. Twenty RYGB patients received 10-mg oral solution oxycodone or 20-mg controlled-release (water-swellable or lipid-based) oxycodone in a three-way, randomised, semiblinded and cross-over study. Blood sampling and pupillary recordings were conducted over a 24-h period. A previously established pharmacokinetic-pharmacodynamic model of these three formulations in healthy volunteers was used in the analysis as a reference model. No differences in absorption kinetics were seen between controlled-release formulations in patients. However, the absorption lag time was 11.5 min in patients vs 14 min in healthy volunteers for controlled-release tablets (P 
Original languageEnglish
JournalBasic & Clinical Pharmacology & Toxicology
Volume129
Issue number3
Pages (from-to)232-245
ISSN1742-7835
DOIs
Publication statusPublished - Sept 2021
Externally publishedYes

Keywords

  • Roux-en-Y gastric bypass
  • oral controlled-release formulation
  • oral solution
  • oxycodone
  • pharmacokinetic-pharmacodynamic modelling
  • Gastric Bypass/adverse effects
  • Oxycodone/pharmacokinetics
  • Administration, Oral
  • Humans
  • Middle Aged
  • Male
  • Analgesics, Opioid/pharmacokinetics
  • Random Allocation
  • Cross-Over Studies
  • Delayed-Action Preparations/pharmacokinetics
  • Aged, 80 and over
  • Adult
  • Female
  • Aged

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