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

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.

Opioid Analgesics after Bariatric Surgery: A Scoping Review to Evaluate Physiological Risk Factors for Opioid-Related Harm

“…Controlled-release oxycodone appeared to be absorbed in a shorter period (T max 11.5 min versus 14 min) in RYGB patients compared to healthy volunteers at 1 year post-surgery. The AUC increased 14.4% [ 60 ]. Contrarily, a PK study on non-obese cancer patients also studied an oral oxycodone prolonged release preparation after total gastrectomy and did not find differences in the PK parameters [ 61 ].…”

New important data concerning problems with substance abuse disorder after bariatric surgery

“…As also reviewed, the alcohol use problem to some extent may reflect pharmacokinetic changes, as well as central changes that are not yet understood. Relative to SUDs, the report mentions that pharmacokinetic problems may also occur over time with morphine [5], although other reports concerning opioids have not adequately clarified this issue [6,7]. However, psychosocial problems after bariatric surgery must also be considered [8], including persistence of medical comorbidities after surgery and lack of adequate improvement in quality of life or physical mobility, previously discussed in depth in a paper addressing suicide risk [9].…”