Single-dose and steady-state pharmacokinetics and pharmacodynamics of oxycodone in patients with cancer

Abstract

The single-dose and steady-state pharmacokinetics and pharmacodynamics of oxycodone have been determined in patients with moderate to severe cancer pain. The mean +/- SD elimination half-life after single-dose administration of intravenous (4.6 mg to 9.1 mg) and oral (9.1 mg) oxycodone was 3.01 +/- 1.37 hours and 3.51 +/- 1.43 hours, respectively. After intravenous administration, the mean +/- SD volume of distribution was 211.9 +/- 186.6 L, and the mean +/- SD total plasma clearance was 48.6 +/- 26.5 L/hr. The mean absolute oral bioavailability of oxycodone was 87%, and the mean +/- SD volume of distribution after oral administration was 249.1 +/- 204.3 L. When administered orally as 10 mg oxycodone hydrochloride every 4 hours, there was no accumulation of oxycodone at steady state and the mean +/- SD steady-state concentration was 34.6 +/- 10.3 micrograms/L. Intravenous oxycodone produced a faster onset of pain relief than oxycodone tablets, but the duration of analgesia was approximately the same (4 hours). However, the incidence of side effects and their severity were significantly higher (p < 0.05) for intravenous oxycodone than for oxycodone tablets. The marked interindividual variation observed in the pharmacokinetics and pharmacodynamics of oxycodone in this study supports the need for individualized dosing regimens.

Morphine or Oxycodone in Cancer Pain?

“…Plasma oxycodone concentrations were above the limit of detection (3 ng:ml) even at 0 h and with small daily doses, indicating a slower elimination of oxycodone, consistent with the longer elimination half-life (t 1:2) and better bioavailability of oral oxycodone compared with morphine reported in previous studies (12,22).…”

“…A wide individual variability in the plasma opioid concentrations was evident, as has been reported in previous studies (17,18,22). In cancer patients, no simple correlation between opioid and metabolite concentrations and pain relief has been found (19), although Faura et al (16) have reported a tendency towards greater stable phase morphine concentrations in cancer patients with optimal pain control.…”

Pharmacokinetics and Variation in the Clearance of Oxycodone and Hydrocotarnine in Patients with Cancer Pain

“…Oxycodone clearance may also be considerably altered with changes in liver blood flow because of the high clearance of 46.8 l/h (ϭ780 ml/min), 16) and accordingly it is expected to decrease when hepatic blood flow is impaired. However, taking account of the high bioavailability of 60% 18) and 87%, 19) the oxycodone clearance, a metabolized amount of oxycodone, is overestimated and unlikely to be that large. Furthermore, changes in liver metabolic enzyme activity can have some effects on oxycodone clearance.…”

Characterization and validation of a pharmacokinetic model for controlled‐release oxycodone

“…Once peak plasma concentrations cation limit of oxycodone in plasma samples was are reached, oxycodone concentrations rapidly decline, 0.2 ng ml−1, with standard curve linearity between with an apparent terminal half-life ranging from 3.0 to 0.2 ng ml−1 and 100 ng ml−1. Inter-day and intra-day 5.7 h [ 5,7]. Because oxycodone is rapidly absorbed precision (expressed as per cent coefficient of variation) and quickly eliminated after oral administration, freranged from 0.4% to 9.9% for nominal standards quent dosing (every 4-6 h) is required to maintain ranging from 0.2 ng ml−1 to 100 ng ml−1.…”

“…The popuate-release oral solution is rapid and could be described lation mean pharmacokinetic parameters obtained by a simple first order absorption process with a lag describe the response in the typical (mean) individual. time: [ 5,7].…”