Monitoring oxycodone use in patients with chronic pain: Analysis of oxycodone and metabolite excretion in saliva and urine
DOI:
https://doi.org/10.5055/jom.2014.0191Keywords:
oxycodone, noroxycodone, metabolism, excretion, salivaAbstract
Objective: Saliva is purported to have a close correspondence to plasma concentrations due to a passive diffusion process from plasma to saliva. However, limited data are available characterizing oxycodone and its metabolites in saliva. The purpose of this analysis was to evaluate the use of saliva monitoring in patients prescribed oxycodone and to compare the disposition of oxycodone in saliva and urine.
Design: This retrospective analysis examined deidentified urine and saliva specimens collected from patients with chronic pain. These specimens were received at Millennium Laboratories between March and June 2012 and analyzed using LCMS/ MS to quantitate oxycodone, noroxycodone, and oxymorphone concentrations.
Results: The geometric mean metabolic ratio (MR) of noroxycodone to oxycodone in saliva was 0.11, whereas the geometric mean MR in urine was 1.7. The geometric mean oxycodone concentration in saliva was 860 ng/mL (range, 1.5-8,600,000 ng/mL; 95% CI, 770-950 ng/mL), whereas the geometric mean noroxycodone concentration was 98 ng/mL (range, 2.3-8,800 ng/mL; 95% CI, 90-107 ng/mL). Fifty-four of the saliva specimens (6 percent) had oxycodone concentrations between 10,000 and 9,000,000 ng/mL.
Conclusions: Oxycodone is predominant over noroxycodone in saliva (similar to plasma), while the reverse relationship exists in urine. Much greater oxycodone concentrations were found in saliva than are expected in plasma (up to a 1,000-fold difference). Saliva concentrations are lower than urine concentrations but still may not reflect plasma disposition. Possible explanations include medication residue in the mouth (recent medication use or misuse) or active secretion into saliva. Saliva analysis may be used for qualitative drug monitoring of oxycodone, with detection rates similar to urine; however, further characterization is needed for appropriate interpretation.
References
Lalovic B, Phillips B, Risler LL, et al.: Quantitative contribution of CYP2D6 and CYP3A to oxycodone metabolism in human liver and intestinal microsomes. Drug Metab Dispos. 2004; 32(4): 447-454.
Lalovic B, Kharasch E, Hoffer C, et al.: Pharmacokinetics and pharmacodynamics of oral oxycodone in healthy human subjects: Role of circulating active metabolites. Clin Pharmacol Ther. 2006; 79(5): 461-479.
Baselt RC: Disposition of Toxic Drugs and Chemicals in Man. 9th ed. Seal Beach, CA: Biomedical Publications, 2011.
Al-Asmari AI, Anderson RA, Cooper GA: Oxycodone-related fatalities in the west of Scotland. J Anal Toxicol. 2009; 33(8): 423-432.
Baker DD, Jenkins AJ: A comparison of methadone, oxycodone, and hydrocodone related deaths in Northeast Ohio. J Anal Toxicol. 2008; 32(2): 165-171.
The DAWN Report: Highlights of the 2010 Drug Abuse Warning Network (DAWN) Findings on Drug-Related Emergency Department Visits. Rockville, MD: Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality, 2012.
Spiller HA: Postmortem oxycodone and hydrocodone blood concentrations. J Forensic Sci. 2003; 48(2): 429-431.
Vearrier D, Curtis JA, Greenberg MI: Biological testing for drugs of abuse. EXS. 2010; 100: 489-517.
Cone EJ, Huestis MA: Interpretation of oral fluid tests for drugs of abuse. Ann N Y Acad Sci. 2007; 1098: 51-103.
Yee DA, Best BM, Atayee RS, et al.: Observations on the urine metabolic ratio of oxymorphone to oxycodone in pain patients. J Anal Toxicol. 2012; 36(4): 232-238.
Allen KR: Screening for drugs of abuse: Which matrix, oral fluid or urine? Ann Clin Biochem. 2011; 48(Pt 6): 531-541.
Verstraete AG: Detection times of drugs of abuse in blood, urine, and oral fluid. Ther Drug Monit. 2004; 26(2): 200.
Hardy J, Norris R, Anderson H, et al.: Is saliva a valid substitute for plasma in pharmacokinetic studies of oxycodone and its metabolites in patients with cancer? Support Care Cancer. 2012; 20(4): 767-772.
O’Neal CL, Crouch DJ, Rollins DE, et al.: Correlation of saliva codeine concentrations with plasma concentrations after oral codeine administration. J Anal Toxicol. 1999; 23(6): 452-459.
Kim I, Barnes AJ, Oyler JM, et al.: Plasma and oral fluid pharmacokinetics and pharmacodynamics after oral codeine administration. Clin Chem. 2002; 48(9): 1486-1496.
Drummer OH: Drug testing in oral fluid. Clin Biochem Rev. 2006; 27(3): 147-159.
Ryan M, Grim SA, Miles MV, et al.: Correlation of lamotrigine concentrations between serum and saliva. Pharmacotherapy. 2003; 23(12): 1550-1557.
Mummert A, Terrell AR, Moore C: Detection of morphine in oral fluid vs. whole blood in chronic pain patients. Paper presented at SOFT, Boston, MA, July 2012.
Ghimenti S, Lomonaco T, Onor M, et al.: Measurement of warfarin in the oral fluid of patients undergoing anticoagulant oral therapy. PLoS One. 2011; 6(12): e28182.
Mullangi R, Agrawal S, Srinivas NR: Measurement of xenobiotics in saliva: Is saliva an attractive alternative matrix? Case studies and analytical perspectives. Biomed Chromatogr. 2009; 23(1): 3-25.
Heltsley R, Depriest A, Black DL, et al.: Oral fluid drug testing of chronic pain patients. II. Comparison of paired oral fluid and urine specimens. J Anal Toxicol. 2012; 36(2): 75-80.
Haeckel R, Hanecke P: Application of saliva for drug monitoring. An in vivo model for transmembrane transport. Eur J Clin Chem Clin Biochem. 1996; 34(3): 171-191.
Vindenes V, Lund HM, Andresen W, et al.: Detection of drugs of abuse in simultaneously collected oral fluid, urine and blood from Norwegian drug drivers. Forensic Sci Int. 2012; 219(1-3): 165-171.
Tuyay J, Coulter C, Rodrigues W, et al.: Disposition of opioids in oral fluid: Importance of chromatography and mass spectral transitions in LC-MS/MS. Drug Test Anal. 2012; 4(6): 395-401.
Moore C, Kelley-Baker T, Lacey J: Interpretation of oxycodone concentrations in oral fluid. J Opioid Manag. 2012; 8(3): 161-166.
Cook JD, Caplan YH, LoDico CP, et al.: The characterization of human urine for specimen validity determination in workplace drug testing: A review. J Anal Toxicol. 2000; 24(11043663): 579-588.
Pesce A, West C, West R, et al.: Determination of medication cutoff values in a pain patient population. J Opioid Manag. 2011; 7(2): 117-122.
Cone EJ, Zichterman A, Heltsley R, et al.: Urine testing for norcodeine, norhydrocodone, and noroxycodone facilitates interpretation and reduces false negatives. Forensic Sci Int. 2010; 198(1-3): 58-61.
Crouch DJ: Oral fluid collection: The neglected variable in oral fluid testing. Forensic Sci Int. 2005; 150(2): 165-173.
O’Neal CL, Crouch DJ, Rollins DE, et al.: The effects of collection methods on oral fluid codeine concentrations. J Anal Toxicol. 2000; 24(7): 536-542.
Dickinson RG, Hooper WD, King AR, et al.: Fallacious results from measuring salivary carbamazepine concentrations. Ther Drug Monit. 1985; 7(1): 41-45.
Uematsu T, Yamaoka M, Matsuura T, et al.: P-glycoprotein expression in human major and minor salivary glands. Arch Oral Biol. 2001; 46(6): 521-527.
Hassan HE, Myers AL, Lee IJ, et al.: Oxycodone induces overexpression of P-glycoprotein (ABCB1) and affects paclitaxel’s tissue distribution in Sprague Dawley rats. J Pharm Sci. 2007; 96(9): 2494-2506.
Bostrom E, Simonsson US, Hammarlund-Udenaes M: Oxycodone pharmacokinetics and pharmacodynamics in the rat in the presence of the P-glycoprotein inhibitor PSC833. J Pharm Sci. 2005; 94(5): 1060-1066.
Yamahara H, Lee VHL: Drug metabolism in the oral cavity. Adv Drug Deliv Rev. 1993; 12(1-2): 25-39.
Zhou LX, Pihlstrom B, Hardwick JP, et al.: Metabolism of phenytoin by the gingiva of normal humans: The possible role of reactive metabolites of phenytoin in the initiation of gingival hyperplasia. Clin Pharmacol Ther. 1996; 60(2): 191-198.
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