Population Pharmacokinetics of Oxycodone and Metabolites in Patients with Cancer-Related Pain

Abstract

Oxycodone is frequently used for treating cancer-related pain, while not much is known about the factors that influence treatment outcomes in these patients. We aim to unravel these factors by developing a population-pharmacokinetic model to assess the pharmacokinetics of oxycodone and its metabolites in cancer patients, and to associate this with pain scores, and adverse events. Hospitalized patients with cancer-related pain, who were treated with oral oxycodone, could participate. Pharmacokinetic samples and patient-reported pain scores and occurrence and severity of nine adverse events were taken every 12 h. In 28 patients, 302 pharmacokinetic samples were collected. A one-compartment model for oxycodone and each metabolite best described oxycodone, nor-oxycodone, and nor-oxymorphone pharmacokinetics. Furthermore, oxycodone exposure was not associated with average and maximal pain scores, and oxycodone, nor-oxycodone, and nor-oxymorphone exposure were not associated with adverse events (all p > 0.05). This is the first model to describe the pharmacokinetics of oxycodone including the metabolites nor-oxycodone and nor-oxymorphone in hospitalized patients with cancer pain. Additional research, including more patients and a more timely collection of pharmacodynamic data, is needed to further elucidate oxycodone (metabolite) pharmacokinetic/pharmacodynamic relationships. This model is an important starting point for further studies to optimize oxycodone dosing regiments in patients with cancer-related pain.

A rapid and sensitive LC–MS/MS method for quantifying oxycodone, noroxycodone, oxymorphone and noroxymorphone in human plasma to support pharmacokinetic drug interaction studies of oxycodone

“…Agema et al studied the pharmacokinetics of oxycodone using an analytical method with a sensitivity of 0.200 μg/L for oxycodone and oxymorphone and 1.00 μg/L for noroxycodone and noroxymorphone with an overall cycle time of 10 min. Both the run time and sensitivity were inferior to those of our method (Agema et al, 2021). Lastly, Gaudette et al (2016) developed an LC–MS/MS method to quantify oxycodone, noroxycodone and oxymorphone concentrations but the quantification of noroxymorphone was not included.…”

Substrates of the Human Brain Proton-Organic Cation Antiporter and Comparison with Organic Cation Transporter 1 Activities

“…For instance, varenicline, an H + OC antiporter substrate [ 28 ], has blood concentrations varying by more than 100-fold in published studies [ 29 ]. Similarly, oxycodone is a well-established substrate of the H + OC antiporter [ 13 ] and pharmacokinetics and pharmacodynamics of oxycodone also showed an extreme interindividual variation [ 30 ]. Clonidine may serve as a third example of a H + OC antiporter substrate with highly variable pharmacokinetics and pharmacodynamics [ 12 ].…”

New light on ω-3 polyunsaturated fatty acids and diabetes debate: a population pharmacokinetic-pharmacodynamic modelling and intake threshold study

“…PPK-PD allows precise analysis of the quantitative relationship between the analyte plasma concentration and the primary efficacy index in patients by establishing a mathematical formula, which includes the quantitative impact of demographic, clinical information, and other covariates [ 17 ]. PPK-PD has been successfully applied to drugs such as acyclovir [ 18 ], vedolizumab [ 19 ], Oxycodone [ 20 ], teicoplanin [ 21 ], providing valuable information for rational clinical use. However, there is still no literature on PPK-PD of nutritional elements, including ω-3 PUFA, which is a major deficiency in precision nutrition.…”