Ladebo, L.Abuhelwa, A.Y.Foster, D.J.R.Kroustrup, J.P.Pacyk, G.J.Kongstad, K.T.Drewes, A.M.Christrup, L.L.Olesen, A.E.2025-12-182025-12-182021Basic and Clinical Pharmacology and Toxicology, 2021; 129(3):232-2451742-78351742-7843https://hdl.handle.net/11541.2/148124The 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 < 0.001). Furthermore, oral bioavailability was 14.4% higher in patients compared to healthy volunteers regardless of formulation type (P < 0.001). Oxycodone pharmacodynamics were not significantly affected by formulation or patient status. However, baseline pupil diameter was inversely correlated with age (P < 0.001) and plasma concentrations of oxycodone at half-maximum effect were 31% lower in males compared to females (P < 0.05). Generic substitution of monophasic lipid-based and water-swellable controlled-release oxycodone tablets may be considered safe in RYGB patients.enCopyright 2021 Nordic Association for the Publication of BCPTHumansOxycodoneAnalgesics, OpioidDelayed-Action PreparationsGastric BypassAdministration, OralCross-Over StudiesRandom AllocationAdultAgedAged, 80 and overMiddle AgedFemaleMaleJournal article10.1111/bcpt.136342-s2.0-85109417461Foster, D.J.R. [0000-0002-7345-4084]