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EACPT Virtual Meeting2021 Markus Zeitlinger2021 год

EACPT Virtual Meeting 2021
статья из журнала

Полный текстСтраница публикацииПубликация в OpenAlex
Аннотация: Background: Cancer-related pain is common and oxycodone is frequently used as treatment in this setting.It is largely unknown which factors affect the outcomes of treatment.Unraveling these factors may be a starting point for precision dosing of oxycodone in this population.Objectives: Our first aim was to develop a model to assess the pharmacokinetics (PK) of oxycodone and its metabolites and the influence of covariates in patients with cancer-related pain.The second aim was to assess the correlation between oxycodone (metabolite) area under the curve (AUC), pain control and adverse events.Methods: Patients with cancer-related pain hospitalized at the Erasmus Medical Center between 2010 and 2014, who were titrated with extended (ER) and/or immediate release (IR) oral oxycodone participated.PK samples of oxycodone, oxymorphone, nor-oxycodone and nor-oxymorphone were taken every 12 h and occasionally at 5, 15, 30 and 60 min after oxycodone IR administration.Patient-reported pain scores and the occurrence and severity of adverse events were collected every 12 h.PK data was analyzed using NONMEM® v7.4.PK/pharmacodynamic (PK/PD) associations were tested using Pearson's correlation coefficient.Results: In total, 1235 samples for oxycodone and its metabolites were collected in 28 patients.A five-compartment model best described oxycodone, nor-oxycodone and nor-oxymorphone pharmacokinetics.Oxycodone absorption was described by 2 separate first-order processes for oxycodone ER and IR tablets.As 58 percent of oxymorphone samples, also an active metabolite, were below the limit of quantification, oxymorphone could not be implemented in the model.None of the tested covariates significantly improved the PK model.Oxycodone AUC and pain scores were correlated; most likely because oxycodone dose was increased when patients reported higher pain scores.Oxycodone, nor-oxycodone and nor-oxymorphone AUC could not be associated with changes in pain scores or adverse events.Conclusion: This is the first study to successfully describe oxycodone, nor-oxycodone and nor-oxymorphone pharmacokinetics using population PK modelling in a real-world population of cancer patients.Additional research, including more patients and denser collection of PD data, is necessary to further elucidate oxycodone (metabolite) PK/ PD relationships to protect patients with cancer-related pain.
Год издания: 2021
Авторы: Markus Zeitlinger
Издательство: Springer Science+Business Media
Источник: European Journal of Clinical Pharmacology
Другие ссылки: European Journal of Clinical Pharmacology (PDF)
European Journal of Clinical Pharmacology (HTML)
PubMed Central (HTML)