Pharmacokinetic‐pharmacodynamic modeling of morphine and oxycodone concentrations and analgesic effect in a multimodal experimental pain model

C Staahl, R Upton, DJR Foster… - The Journal of …, 2008 - Wiley Online Library
C Staahl, R Upton, DJR Foster, LL Christrup, K Kristensen, SH Hansen, L Arendt‐Nielsen
The Journal of Clinical Pharmacology, 2008Wiley Online Library
Analgesia from most opioids is mediated by μ receptors located mainly in the central
nervous system. Previous studies have shown a different pharmacological profile of
oxycodone in respect to visceral analgesia. This study investigated if morphine and
oxycodone have different pharmacokinetic/pharmacodynamic profiles, in particular with
respect to delay between opioid blood concentration and analgesia. Twenty‐four healthy
subjects had oral morphine (30 mg), oxycodone (15 mg), or placebo. Mechanical, thermal …
Analgesia from most opioids is mediated by μ receptors located mainly in the central nervous system. Previous studies have shown a different pharmacological profile of oxycodone in respect to visceral analgesia. This study investigated if morphine and oxycodone have different pharmacokinetic/pharmacodynamic profiles, in particular with respect to delay between opioid blood concentration and analgesia. Twenty‐four healthy subjects had oral morphine (30 mg), oxycodone (15 mg), or placebo. Mechanical, thermal, and electrical pain tests were performed in the skin and viscera. Blood samples and pain measurements were taken at baseline and after 15, 30, 60, 90, and 120 minutes. Pharmacokinetic/pharmacodynamic profiles were modeled using a 2‐stage, nonlinear, mixed‐effects approach with an effect compartment to represent the concentration‐analgesia delay. Morphine kinetics was best described by a 2‐compartment model, whereas oxycodone kinetics was best described with a 1‐compartment model. Generally the analgesic effects of morphine were best related to plasma concentration by introducing a delay via an effect compartment. However, for oxycodone, this was only the case for analgesia in the somatic pain measures, whereas the plasma concentration correlated better to the course of the analgesia with no delay in the visceral pain measures. Oxycodone and morphine showed different pharmacodynamic/pharmacokinetic relationships for the visceral analgesia, whereas relationships were alike for somatic analgesia.
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