Effect of Roux-en-Y gastric bypass on the pharmacokinetic-pharmacodynamic relationships of liquid and controlled-release formulations of oxycodone
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Effect of Roux-en-Y gastric bypass on the pharmacokinetic-pharmacodynamic relationships of liquid and controlled-release formulations of oxycodone. / Ladebo, Louise; Abuhelwa, Ahmad Y.; Foster, David J.R.; Kroustrup, Jens P.; Pacyk, Grzegorz J.; Kongstad, Kenneth T.; Drewes, Asbjørn M.; Christrup, Lona L.; Olesen, Anne E.
I: Basic and Clinical Pharmacology and Toxicology, Bind 129, Nr. 3, 2021, s. 232-245.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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 -
ID: 286500983