TY - JOUR

T1 - Effect of Roux-en-Y gastric bypass on the pharmacokinetic-pharmacodynamic relationships of liquid and controlled-release formulations of oxycodone

AU - Ladebo, Louise

AU - Abuhelwa, Ahmad Y.

AU - Foster, David J.R.

AU - Kroustrup, Jens P.

AU - Pacyk, Grzegorz J.

AU - Kongstad, Kenneth T.

AU - Drewes, Asbjørn M.

AU - Christrup, Lona L.

AU - Olesen, Anne E.

N1 - Funding Information: The Talent Management Programme, Aalborg University, the Oticon Foundation and the Augustinus Foundation are acknowledged for supporting this study financially. Isabelle Myriam Larsen is acknowledged for her contribution with regard to data collection. Charlotte Skov at the Department of Clinical Medicine and Endocrinology, Aalborg University Hospital, is acknowledged for her contribution regarding patient recruitment. Arife ?nder is acknowledged for her contribution to sample preparation for the quantitative analyses. DJR Foster, AY Abuhelwa and RN Upton acknowledge that the Australian Centre for Pharmacometrics is an initiative of the Australian Government as part of the National Collaborative Research Infrastructure Strategy. Funding Information: The Talent Management Programme, Aalborg University, the Oticon Foundation and the Augustinus Foundation are acknowledged for supporting this study financially. Isabelle Myriam Larsen is acknowledged for her contribution with regard to data collection. Charlotte Skov at the Department of Clinical Medicine and Endocrinology, Aalborg University Hospital, is acknowledged for her contribution regarding patient recruitment. Arife Önder is acknowledged for her contribution to sample preparation for the quantitative analyses. DJR Foster, AY Abuhelwa and RN Upton acknowledge that the Australian Centre for Pharmacometrics is an initiative of the Australian Government as part of the National Collaborative Research Infrastructure Strategy. Publisher Copyright: © 2021 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society)

PY - 2021

Y1 - 2021

N2 - 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 < 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.

AB - 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 < 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.

KW - oral controlled-release formulation

KW - oral solution

KW - oxycodone

KW - pharmacokinetic-pharmacodynamic modelling

KW - Roux-en-Y gastric bypass

U2 - 10.1111/bcpt.13634

DO - 10.1111/bcpt.13634

M3 - Journal article

C2 - 34228875

AN - SCOPUS:85109417461

VL - 129

SP - 232

EP - 245

JO - Basic and Clinical Pharmacology and Toxicology

JF - Basic and Clinical Pharmacology and Toxicology

SN - 1742-7835

IS - 3

ER -