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Oral Oxycodone (oral + oxycodone)

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Medical Sciences	100%

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Grapefruit Juice Enhances the Exposure to Oral Oxycodone

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2010
Tuija H. Nieminen
The objective of this study was to examine the effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of oral oxycodone in a randomized cross-over study with two phases at an interval of 4 weeks. Twelve healthy volunteers ingested 200 ml of grapefruit juice or water t.i.d. for 5 days. An oral dose of oxycodone hydrochloride 10 mg was administered on day 4. Oxycodone, noroxycodone, oxymorphone and noroxymorphone concentrations were analysed from the plasma samples for 48 hr and behavioural and analgesic effects were recorded for 12 hr. Grapefruit juice increased the mean area under the oxycodone concentration,time curve (AUC0,,) by 1.7-fold (p < 0.001), the peak plasma concentration by 1.5-fold (p < 0.001) and the half-life of oxycodone by 1.2-fold (p < 0.001) as compared to the water. The metabolite-to-parent AUC0,, ratios (AUCm/AUCp) of noroxycodone and noroxymorphone decreased by 44% (p < 0.001) and 45% (p < 0.001), respectively. Oxymorphone AUC0,, increased by 1.6-fold (p < 0.01) after grapefruit juice, but the AUCm/AUCp remained unchanged. Pharmacodynamic changes were modest and only self-reported performance significantly impaired after grapefruit juice. Analgesic effects were not influenced. Grapefruit juice inhibited the CYP3A4-mediated first-pass metabolism of oxycodone, decreased the formation of noroxycodone and noroxymorphone and increased that of oxymorphone. We conclude that dietary consumption of grapefruit products may increase the concentrations and effects of oxycodone in clinical use. [source]

Oral versus Intravenous Opioid Dosing for the Initial Treatment of Acute Musculoskeletal Pain in the Emergency Department

ACADEMIC EMERGENCY MEDICINE, Issue 12 2008
James R. Miner MD
Abstract Objectives:, The objective was to compare the time to medication administration, the side effects, and the analgesic effect at sequential time points after medication administration of an oral treatment strategy using oxycodone solution with an intravenous (IV) treatment strategy using morphine sulfate for the initial treatment of musculoskeletal pain in emergency department (ED) patients. Methods:, This was a prospective randomized clinical trial of patients >6 years old who were going to receive IV morphine sulfate for the treatment of musculoskeletal pain but did not yet have an IV. Consenting patients were randomized to have the treating physician order either 0.1 mg/kg morphine sulfate IV or 0.125 mg/kg oxycodone orally in a 5 mg/5 mL suspension as their initial treatment for pain. The time from the placement of the order to the administration of the medication was recorded. Pain was measured using a 100-mm visual analog scale (VAS) and recorded at 0, 10, 20, 30 and 40 minutes after drug administration. Results:, A total of 405 eligible patients were identified during the study period; 328 (81.0%) patients consented to be in the study. A total of 158 patients were randomized to the IV morphine sulfate treatment group, and 162 were randomized to the oral oxycodone treatment group. Of the patients who were randomized to IV therapy, 34 were withdrawn from the study prior to drug administration; leaving 125 patients in the IV group for analysis. Of the patients who randomized to oral therapy, 22 were withdrawn from the study prior to drug administration, leaving 140 patients for analysis. No serious adverse events were detected. There was a 12-minute difference between the median time of the order and the administration of oral oxycodone (8.5 minutes) and IV morphine (20.5 minutes). The mean percent change in VAS score was larger for patients in the IV therapy group than those in the oral therapy group at 10 and 20 minutes. At 30 and 40 minutes, the authors could no longer detect a difference. The satisfaction scale score was higher after treatment for the morphine group (median = 4; interquartile range [IQR] = 4 to 5) than for the oxycodone group (median = 4; IQR = 2 to 5; p = 0.008). Conclusions:, The oral loading strategy was associated with delayed onset of analgesia and decreased patient satisfaction, but a shorter time to administration. The oral loading strategy using an oxycodone solution provided similar pain relief to the IV strategy using morphine 30 minutes after administration of the drug. Oral 0.125 mg/kg oxycodone represents a feasible alternative to 0.1 mg/kg IV morphine in the treatment of severe acute musculoskeletal pain when difficult or delayed IV placement greater than 30 minutes presents a barrier to treatment. [source]

Exposure to oral oxycodone is increased by concomitant inhibition of CYP2D6 and 3A4 pathways, but not by inhibition of CYP2D6 alone

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2010
Juha Grönlund
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Oxycodone is an opioid analgesic that is metabolized mainly in the liver by cytochrome P450 (CYP) 2D6 and 3A4 enzymes. , So far, the effects of CYP2D6 or CYP3A4 inhibitors on the pharmacokinetics of oxycodone in humans have not been systematically studied. WHAT THIS STUDY ADDS , Drug interactions arising from CYP2D6 inhibition most likely have minor clinical importance for oral oxycodone. , When both of CYP2D6 and CYP3A4 pathways are inhibited, the exposure to oral oxycodone is increased substantially. AIM The aim of this study was to find out whether the inhibition of cytochrome P450 2D6 (CYP2D6) with paroxetine or concomitant inhibition of CYP2D6 and CYP3A4 with paroxetine and itraconazole, altered the pharmacokinetics and pharmacological response of orally administered oxycodone. METHODS A randomized placebo-controlled cross-over study design with three phases was used. Eleven healthy subjects ingested 10 mg of oral immediate release oxycodone on the fourth day of pre-treatment with either placebo, paroxetine (20 mg once daily) or paroxetine (20 mg once daily) and itraconazole (200 mg once daily) for 5 days. The plasma concentrations of oxycodone and its oxidative metabolites were measured for 48 h, and pharmacological (analgesic and behavioural) effects were evaluated. RESULTS Paroxetine alone reduced the area under concentration,time curve (AUC(0,0,48 h)) of the CYP2D6 dependent metabolite oxymorphone by 44% (P < 0.05), but had no significant effects on the plasma concentrations of oxycodone or its pharmacological effects when compared with the placebo phase. When both oxidative pathways of the metabolism of oxycodone were inhibited with paroxetine and itraconazole, the mean AUC(0,,) of oxycodone increased by 2.9-fold (P < 0.001), and its Cmax by 1.8-fold (P < 0.001). Visual analogue scores for subjective drug effects, drowsiness and deterioration of performance were slightly increased (P < 0.05) after paroxetine + itraconazole pre-treatment when compared with placebo. CONCLUSIONS Drug interactions arising from CYP2D6 inhibition most likely have minor clinical importance for oral oxycodone if the function of the CYP3A4 pathway is normal. When both CYP2D6 and CYP3A4 pathways are inhibited, the exposure to oral oxycodone is increased substantially. [source]