J Clin Pharmacol. 2022 Apr 8. doi: 10.1002/jcph.2058. Online ahead of print.
Little is known on how opioid responses vary by age and in the presence of alcohol consumption. This model-based pharmacokinetic-pharmacodynamic (PK-PD) analysis quantified the impact of age and alcohol use on pupillometry and cold pressor test (CPT) PD based on data from an open label study of immediate-release 10 mg oral oxycodone in middle-age and older adults (age 35-85) without severe functional limitations. PK and pupillometry assessments were obtained on 11 occasions over 8 hours. CPT was administered at 1.5, 5 and 8 hours post oxycodone dosing. The study consisted of 62 older adults (age 60+) and 66 middle-age adults (age 35-59), with 82% meeting the unhealthy drinking criteria. Oral oxycodone PK were well described using a one compartment model with a sequential zero to first order absorption process. Recent alcohol use measures were selected a priori. for the analysis. Inhibitory Emax and linear direct effect PD models described the respective pupillometry and CPT data using simultaneous PK-PD analysis in MONOLIX. This analysis demonstrated an influence of age on clearance and bodyweight on the distribution volume of oxycodone, alcohol consumption was not noted to alter oxycodone PK. Oxycodone pupillometry PD were influenced by the level of subject-reported alcohol consumption (AUDIT-C), alcohol use biomarker blood phosphatidylethanol, previous cannabis use, and age. Over the opioid exposure range of the study, none of the covariables including alcohol and age were noted to affect CPT PD. Additional clinical studies are needed to further probe the clinical consequences of opioid-alcohol-age interaction. This article is protected by copyright. All rights reserved.
Source: ncbi 2