Abstract
Purpose
To characterize the pharmacokinetics (PK) of oxycodone following intravenous injection and administration of three oral dosage forms (solution, capsule, and controlled-release tablet) in elderly patients (age 76–89 years) undergoing cystoscopy.
Methods
This was an open, randomized study with two sequences and two visits in 15 elderly patients. The patients were given intravenous injection (over 10 min) of 5 mg of oxycodone hydrochloride trihydrate. Oxycodone hydrochloride (5 mg in all forms) was orally administered as a solution, a capsule, and a controlled-release tablet. Venous blood samples were collected up to 17 h after oxycodone administration. Population PK parameters were calculated with NONMEM VI 2.0. For intravenous injection we calculated clearance, volume of distribution at steady state, and the half-life of elimination, and for oral dosage forms also the absolute bioavailability.
Results
Clearance of the intravenous injections was 28.9 L/h; the volume of distribution at steady state and the half-life of elimination were 186 L and 5.2 h, respectively. The absolute bioavailability of oxycodone was 59 % from oral solutions, 64 % from capsules, and 55 % from controlled-release tablets.
Conclusions
Our results indicate that, in the elderly, the bioavailability of the three different oral dosage forms of oxycodone is fairly similar.
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References
Kalso E (2005) Oxycodone. J Pain Symptom Manage 29:47S–56S
Kokki H, Rasanen I, Reinikainen M, Suhonen P, Vanamo K, Ojanperä I (2004) Pharmacokinetics of oxycodone after intravenous, buccal, intramuscular and gastric administration in children. Clin Pharmacokinet 43:613–622
Cusack B (2004) Pharmacokinetics in older persons. Am J Geriatr Pharmacother 2:274–302
Liukas A, Kuusniemi K, Aantaa R, Virolainen P, Neuvonen M, Neuvonen PJ, Olkkola KT (2011) Elimination of intravenous oxycodone in the elderly: a pharmacokinetic study in postoperative orthopaedic patients of different age groups. Drug Aging 28:41–50
Aubrun F, Marmion F (2007) The elderly patient and postoperative pain treatment. Best Pract Res Clin Anaesthesiol 21:109–127
McLean AJ, Le Couteur DG (2004) Aging biology and geriatric clinical pharmacology. Pharmacol Rev 56:163–184
Gislason GH, Rasmussen JN, Abildstrom SZ, Schramm TK, Hansen ML, Fosbøl EL et al (2009) Increased mortality and cardiovascular morbidity associated with use of nonsteroidal anti-inflammatory drugs in chronic heart failure. Arch Intern Med 169:141–149
Turnheim K (2005) Pharmacokinetic dosage guidelines for elderly subjects. Expert Opin Drug Metab Toxicol 1:33–48
Kaestli LZ, Wasilewski-Rasca AF, Bonnabry P, Vogt-Ferrier N (2008) Use of transdermal drug formulations in the elderly. Drugs Aging 25:269–280
Fleisher LA (2010) Risk of anesthesia. In: Miller RD, Eriksson LI, Fleisher LA, Wiener-Kronish JP, Young WL (eds) Miller’s anesthesia, 7th edn. Elsevier, Philadelphia, pp 969–999
Kokki H, Rasanen I, Laisalmi M, Lehtola S, Ranta VP, Vanamo K, Ojanperä I (2006) Comparison of oxycodone pharmacokinetics after buccal and sublingual administration in children. Clin Pharmacokinet 45:745–754
Jonsson EN, Karlsson MO (1999) Xpose—an S-PLUS based population pharmacokinetic/pharmacodynamic model building aid for NONMEM. Comput Methods Programs Biomed 58:51–64
Mandema JW, Kaiko RF, Oshlack B, Reder RF, Stanski DR (1996) Characterization and validation of a pharmacokinetic model for controlled-release oxycodone. Br J Clin Pharmacol 42:747–756
Beal SL (2001) Ways to fit a PK model with some data below the quantification limit. J Pharmacokinet Pharmacodyn 28:481–504
Nieminen TH, Hagelberg NM, Saari TI, Pertovaara A, Neuvonen M, Laine K, Neuvonen PJ, Olkkola KT (2009) Rifampin greatly reduces the plasma concentrations of intravenous and oral oxycodone. Anesthesiology 110:1371–1378
Leow KP, Smith MT, Williams B, Cramond T (1992) Single-dose and steady-state pharmacokinetics and pharmacodynamics of oxycodone in patients with cancer. Clin Pharmacol Ther 52:487–495
Pöyhiä R, Olkkola KT, Seppälä T, Kalso E (1991) The pharmacokinetics of oxycodone after intravenous injection in adults. Br J Clin Pharmacol 32:516–518
Takala A, Kaasalainen V, Seppälä T, Kalso E, Olkkola KT (1997) Pharmacokinetic comparison of intravenous and intranasal administration of oxycodone. Acta Anaesthesiol Scand 41:309–312
Leow KP, Cramond T, Smith MT (1995) Pharmacokinetics and pharmacodynamics of oxycodone when given intravenously and rectally to adult patients with cancer pain. Anesth Analg 80:296–302
Liukas A, Kuusniemi K, Aantaa R, Virolainen P, Neuvonen M, Neuvonen PJ, Olkkola KT (2008) Plasma concentrations of oral oxycodone are greatly increased in the elderly. Clin Pharmacol Ther 84:462–467
Villesen HH, Banning AM, Petersen RH, Weinelt S, Poulsen JB, Hansen SH, Christrup LL (2007) Pharmacokinetics of morphine and oxycodone following intravenous administration in elderly patients. Ther Clin Risk Manag 3:961–967
Zimmer AW, Calkins E, Hadley E, Ostfeld AM, Kaye JM, Kaye D (1985) Conducting clinical research in geriatric populations. Ann Intern Med 103:276–283
Acknowledgments
The authors would like to thank V.-P. Ranta, PhD (pharm), A. Kuosmanen, BSc (pharm), H. Nordman, MD, and S. Savinainen, MD, for their help in conducting the study.
The authors have no conflicts of interest to report regarding the content of this manuscript. The study did not receive financial support from any external source.
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Some of the study results were presented as an abstract at the Pain Congress, 7th Congress of the European Federation of IASP® Chapters (EFIC®) in Hamburg, Germany, September 2011.
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Kokki, M., Välitalo, P., Rasanen, I. et al. Absorption of different oral dosage forms of oxycodone in the elderly: a cross-over clinical trial in patients undergoing cystoscopy. Eur J Clin Pharmacol 68, 1357–1363 (2012). https://doi.org/10.1007/s00228-012-1267-9
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DOI: https://doi.org/10.1007/s00228-012-1267-9