Effect of Roux-en-Y gastric bypass on the pharmacokinetic-pharmacodynamic relationships of liquid and controlled-release formulations of oxycodone.
Basic Clin Pharmacol Toxicol
; 129(3): 232-245, 2021 Sep.
Article
en En
| MEDLINE
| ID: mdl-34228875
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 < 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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Oxicodona
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Derivación Gástrica
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Preparaciones de Acción Retardada
Tipo de estudio:
Clinical_trials
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Basic Clin Pharmacol Toxicol
Asunto de la revista:
FARMACOLOGIA
/
TOXICOLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Dinamarca