Pharmacokinetics and Pharmacodynamics of Oxycodone When Given Intravenously and Rectally to Adult Patients with Cancer Pain

Abstract

The single-dose pharmacokinetics and pharmacodynamics of oxycodone administered by the intravenous and rectal routes were determined in 12 adult cancer patients with moderate to severe cancer pain (visual analog scale [VAS] score, approximately 5). Oxycodone was administered by the intravenous and rectal routes with open drug administration and a cross-over design. After single-dose intravenous administration (7.9 +/- 1.5 mg, mean +/- SD), the mean (+/- SD) terminal half-life was 3.4 h (+/- 1.1), the mean (+/- SD) plasma clearance was 45.4 L/h (+/- 10.1), and the mean (+/- SD) volume of distribution in the terminal phase was 3.0 L/kg (+/- 1.1). After rectal oxycodone (30 mg), the mean (+/- SD) absorption lag time was 0.52 h (+/- 0.29) and the mean (+/- SD) absolute bioavailability was 61.6% (+/- 30.2%). Intravenous oxycodone was associated with a rapid onset of pain relief (5-8 min) in contrast to the 0.5- to 1.0-h delay observed after rectal administration. However, rectal oxycodone provided analgesia of much longer duration (approximately 8-12 h) than did intravenous oxycodone (approximately 4 h). There were no significant differences (P > 0.05) in the incidence and severity of side effects between intravenous and rectal oxycodone. The marked interindividual variation observed in the pharmacokinetics and pharmacodynamics of oxycodone in this study emphasizes the need for individualized dosing regimens.

Analysis of oxycodol and noroxycodol stereoisomers in biological samples by capillary electrophoresis

“…NaBH 4 was a kind gift of the Fachhochschule of Burgdorf, Switzerland. Sodium acetate, NH 4 Cl, KOH, ammonia, and isopropanol were all of 'per analysis' grade and were from Merck (Darmstadt, Germany). Methanol (HPLC supra-gradient-grade) and dichloromethane (HPLC-grade) were purchased from Biosolve (Valkenswaard, The Netherlands).…”

“…280 mg NaBH 4 was added and the solution was left at room temperature for 5 h and periodically stirred. Thereafter, 0.5 mL of a saturated solution of NH 4 Cl was added and a precipitation of white crystals was observed. Everything could be redissolved via addition of 0.5 mL water.…”

Normal-release and controlled-release oxycodone: pharmacokinetics, pharmacodynamics, and controversy

“…The mean absorption lag time is slightly longer than that of oral oxycodone (0.52-0.76 h) [6,7]. Bioavailability of rectal oxycodone is 61.6±30.2%, which is the same as for oral oxycodone [7,23].…”

“…The mean elimination half-life of rectal oxycodone is 5.4 h (± 1.19 h), and the AUC is equivalent to that following oral administration [6,7]. The mean absorption lag time is slightly longer than that of oral oxycodone (0.52-0.76 h) [6,7].…”

“…The mean lag time from oral administration to pharmacodynamic effect (analgesia) is 0.52±0.33 h [5]. The half-life is not influenced by the route of administration (intravenous, rectal or oral) [6,7]. At physiological pH and temperature, in vitro serum protein binding is 38-45%, as against 85% for fentanyl and 35% for morphine [8].…”