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Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 1/2000

01-01-2000 | Review Article

Clinical Pharmacokinetics of Transdermal Opioids

Focus on Transdermal Fentanyl

Authors: Dr Stefan Grond, Lukas Radbruch, Klaus A. Lehmann

Published in: Clinical Pharmacokinetics | Issue 1/2000

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Abstract

Transdermal delivery allows continuous systemic application of opioids through the intact skin. This review analyses the pharmacokinetic properties of transdermal opioid administration in the context of clinical experience, with a focus on fentanyl.
A transdermal therapeutic system (TTS) for fentanyl has been developed. The amount of fentanyl released is proportional to the surface area of the TTS, which is available in different sizes. After the first application of a TTS, a fentanyl depot concentrates in the upper skin layers and it takes several hours until clinical effects are observed. The time from application to minimal effective and maximum serum concentrations is 1.2 to 40 hours and 12 to 48 hours, respectively. Steady state is reached on the third day, and can be maintained as long as patches are renewed. Within each 72-hour period, serum concentrations decrease gradually over the second and third days. When a TTS is removed, fentanyl continues to be absorbed into the systemic circulation from the cutaneous depot. The terminal half-life for TTS fentanyl is approximately 13 to 25 hours. The interindividual variability of serum concentrations, partly caused by different clearance rates, is markedly larger than the intraindividual variability.
The effectiveness of TTS fentanyl was first demonstrated in acute postoperative pain. However, the slow pharmacokinetics and large variability of TTS fentanyl, together with the relatively short duration of postoperative pain, precluded adequate dose finding and led to inadequate pain relief or, especially, a high incidence of respiratory depression; such use is now contraindicated. Conversely, in cancer pain, TTS fentanyl offers an interesting alternative to oral morphine, and its effectiveness and tolerability in this indication has been demonstrated by a number of trials. Its usefulness in chronic pain of nonmalignant origin remains to be confirmed in controlled trials.
In general, TTS fentanyl produces the same adverse effects as other opioids, mainly sedation, nausea, vomiting and constipation. In comparison with oral morphine, TTS fentanyl causes fewer gastrointestinal adverse events. The risk of hypoventilation is comparatively low in cancer patients.
Sufentanil and buprenorphine may also be suitable for transdermal delivery, but clinical results are not yet available. Transdermal morphine is only useful if applied to de-epithelialised skin. However, iontophoresis may allow transdermal administration of opioids, including morphine, with a rapid achievement of steady state concentrations and the ability to adjust delivery rates. This would be beneficial for acute and/or breakthrough pain, and initial clinical trials are in progress.
Literature
1.
Lapin J, Houde RW, Kaiko RF, et al. Cancer pain management with a controlled-release oral morphine preparation. J Pain Symptom Manage 1989; 4 (3): 146–51.PubMedCrossRef
2.
Lehmann KA. New developments in patient-controlled postoperative analgesia. Ann Med 1995; 27 (2): 271–82.PubMedCrossRef
3.
Morgan M. The rational use of intrathecal and extradural opioids. Br J Anaesth 1989; 63 (2): 165–88.PubMedCrossRef
4.
Berner B, John VA. Pharmacokinetic characterisation of transdermal delivery systems. Clin Pharmacokinet 1994; 26 (2): 121–34.PubMedCrossRef
5.
Roy SD, Flynn GL. Transdermal delivery of narcotic analgesics: comparative permeabilities of narcotic analgesics through human cadaver skin. Pharm Res 1989; 6 (10): 825–32.PubMedCrossRef
6.
Jeal W, Benfield P. Transdermal fentanyl: a review of its pharmacological properties and therapeutic efficacy in pain control. Drugs 1997; 53 (1): 109–38.PubMedCrossRef
7.
Alexander-Williams JM, Rowbotham DJ. Novel routes of opioid administration. B J Anaesth 1998; 81: 3–7.CrossRef
8.
Kallar S. Introduction: clinical experiences with fentanyl oralet (oral transmucosal fentanyl citrate). Am J Anesth 1997; 24 (1 Suppl.): 4–5.
9.
Gibelli G, Negrini M, Bruno AM, et al. Chronic effects of trans-dermal nitroglycerin in stable angina pectoris: a within-patient, placebo-controlled study. Int J Clin Pharmacol Ther Toxicol 1989; 27 (9): 436–41.PubMed
10.
Johannisson E, Landgren BM, Diczfalusy E. Endometrial and vaginal response to three different oestrogen preparations administered by the transdermal and oral routes. Maturitas 1988; 10 (3): 181–92.PubMedCrossRef
11.
12.
Shupak A, Gordon CR, Spitzer O, et al. Three-years’ experience of transdermal scopolamine: long-term effectiveness and side-effects. Pharmatherapeutica 1989; 5 (6): 365–70.PubMed
13.
Toon S, Hopkins KJ, Aarons L, et al. Rate and extent of absorption of clonidine from a transdermal therapeutic system. J Pharm Pharmacol 1989; 41 (1): 17–21.PubMedCrossRef
14.
Mather LE. Pharmacokinetic and pharmacodynamic factors influencing the choice dose and route of administration of opiates for acute pain. In: Bullingham RES, editor. Opiate analgesia. London: Saunders, 1983: 17–40.
15.
Andrews CJH, Prys-Roberts C. Fentanyl: a review. In: Bullingham RES, editor. Opiate analgesia. London: Saunders, 1983: 97–122.
16.
Mather LE. Clinical pharmacokinetics of fentanyl and its newer derivatives. Clin Pharmacokinet 1983; 8: 422–446.PubMedCrossRef
17.
Scholz J, Steinfath M, Schulz M. Clinical pharmacokinetics of alfentanil, fentanyl and sufentanil: an update. Clin Pharmacokinet 1996; 31 (4): 275–92.PubMedCrossRef
18.
Stanley TH. The history and development of the fentanyl series. J Pain Symptom Manage 1992; 7 Suppl. 3: 3–7.CrossRef
19.
Lehmann KA, Zech D. Transdermal fentanyl: clinical pharmacology. J Pain Symptom Manage 1992; 7 (3 Suppl.): S8–16.PubMedCrossRef
20.
Hwang SS, Nichols KC, Southam M. Transdermal permeation: physiological and physicochemical aspects. In: Lehmann KA, Zech D, editors. Transdermal fentanyl. Berlin: Springer, 1991: 1–7.CrossRef
21.
Roy SD, Hou SY, Witham SL, et al. Transdermal delivery of narcotic analgesics: comparative metabolism and permeability of human cadaver skin and hairless mouse skin. J Pharm Sci 1994; 83 (12): 1723–8.PubMedCrossRef
22.
Varvel JR, Shafer SL, Hwang SS, et al. Absorption characteristics of transdermally administered fentanyl. Anesthesiology 1989; 70 (6): 928–34.PubMedCrossRef
23.
Scheuplein RJ, Blank IH. Permeability of the skin. Physiol Rev 1971; 51 (4): 702–47.PubMed
24.
Southwell D, Barry B, Woodford R. Variations of permeability of human skin within and between specimens. Int J Pharm 1984; 18: 299–309.CrossRef
25.
Shaw JE, Chandrasekaran SK. Transdermal therapeutic symptoms. In: Prescott LF, Nimmo BS, editors. Drug absorption. Balgowlah: ADIS Press, 1981: 186–93.
26.
Roy SD, Flynn GL. Transdermal delivery of narcotic analgesics: pH, anatomical, and subject influences on cutaneous permeability of fentanyl and sufentanil. Pharm Res 1990; 7 (8): 842–7.PubMedCrossRef
27.
Michaels AS, Chandrasekaran SK, Shaw JE. Drug permeation through human skin: theory and in vitro experimental measurement. Am Inst Chem Eng 1975; 21: 985–996.CrossRef
28.
Shaw JE, Theeuwes FR. Transdermal dosage forms. In: Prescott LF, Nimmo WS, editors. Rate control in drug therapy. Edinburgh: Churchill Livingston, 1985: 65–70.
29.
Mather LE, Gourlay GK. Pharmacokinetic of fentanyl. In: Lehmann KA, Zech D, editors. Transdermal fentanyl. Berlin: Springer, 1991: 73–97.CrossRef
30.
Reilly CS, Wood AJJ, Wood M. Variability of fentanyl pharmacokinetics in man. Anaesthesia 1984; 40: 837–843.CrossRef
31.
Gourlay GK, Kowalski SR, Plummer JL, et al. The transdermal administration of fentanyl in the treatment of postoperative pain: pharmacokinetics and pharmacodynamic effects. Pain 1989; 37 (2): 193–202.PubMedCrossRef
32.
Gourlay GK, Kowalski SR, Plummer JL, et al. The efficacy of transdermal fentanyl in the treatment of postoperative pain: a double-blind comparison of fentanyl and placebo systems. Pain 1990; 40 (1): 21–8.PubMedCrossRef
33.
Gourlay GK, Kowalski SR, Plummer JL, et al. Fentanyl blood concentration-analgesic response relationship in the treatment of postoperative pain. Anesth Analg 1988; 67 (4): 329–37.PubMedCrossRef
34.
Durcan TG, Sockalingham I, Hanna MH, et al. Pharmocokinetic study of repeated 72 hour applications of TTS-fentanyl. Br J Anaesth 1995; 74 Suppl. 1: 139.
35.
Broome IJ, Wright BM, Bower S, et al. Postoperative analgesia with transdermal fentanyl following lower abdominal surgery. Anaesthesia 1995; 50 (4): 300–3.PubMedCrossRef
36.
Portenoy RK, Southam MA, Gupta SK, et al. Transdermal fentanyl for cancer pain. Repeated dose pharmacokinetics. Anesthesiology 1993; 78 (1): 36–43.PubMedCrossRef
37.
Duthie DJ, Rowbotham DJ, Wyld R, et al. Plasma fentanyl concentrations during transdermal delivery of fentanyl to surgical patients. Br J Anaesth 1988; 60 (6): 614–8.PubMedCrossRef
38.
Bell SD, Goldberg ME, Larijani GE, et al. Evaluation of trans-dermal fentanyl for multiday analgesia in postoperative patients [abstract]. Anesth Analg 1989; 68 Suppl.: S22.
39.
Bell SD, Goldberg ME. Comparison of single patch multi-day versus multiple patch single day TTS fentanyl [abstract]. Can J Anaesth 1989; 36 Suppl.: S116.
40.
Caplan RA, Ready LB, Oden RV, et al. Transdermal fentanyl for postoperative pain management: a double-blind placebo study. JAMA 1989; 261 (7): 1036–9.PubMedCrossRef
41.
Christensen ML, Wang WC, Harris S, et al. Transdermal fentanyl administration in children and adolescents with sickle cell pain crisis. J Pediatr Hematol Oncol 1996; 18 (4): 372–6.PubMedCrossRef
42.
Collins JJ, Dunkel IJ, Gupta SK, et al. Transdermal fentanyl in children with cancer pain: feasibility, tolerability, and pharmacokinetic correlates. J Pediatr 1999; 134: 319–23.PubMedCrossRef
43.
Hanna MH, Wodding S A. A study to examine repeat dose pharmacokinetics of TTS (fentanyl) using repeated 72-hour applications for a 6 day period in patients with cancer pain or intractable pain requiring opioid therapy. Trial number FEN-GBR-008. Janssen Research Foundation, 1995 [data on file].
44.
Esteve M, Levron JC, Flaisler DB, et al. Does aging modify pharmacokinetics of transdermal fentanyl [abstract]? Anesthesiology 1991; 75 (3A): A705.CrossRef
45.
Grond S, Zech D, Lehmann KA, et al. Transdermal fentanyl in the long-term treatment of cancer pain: a prospective study of 50 patients with advanced cancer of the gastrointestinal tract or the head and neck region. Pain 1997; 69 (1–2): 191–8.PubMedCrossRef
46.
Holley FO, van Steennis C. Postoperative analgesia with fentanyl: pharmacokinetics and pharmacodynamics of constantrate i.V. and transdermal delivery. Br J Anaesth 1988; 60 (6): 608–13.PubMedCrossRef
47.
Latasch L, Luders S. Transdermal fentanyl against postoperative pain. Acta Anaesthesiol Belg 1989; 40 (2): 113–9.PubMed
48.
McLeskey CH. Fentanyl TTS for postoperative analgesia. Eur J Pain 1990; 11: 92–7.
49.
Nimmo WS, Duthie DJR. Plasma fentanyl concentrations after transdermal or i.V. infusion of fentanyl [abstract]. Anesthesiology 1986; 65 (3A): A196.CrossRef
50.
Plezia PM, Kramer TH, Linford J, et al. Transdermal fentanyl: pharmacokinetics and preliminary clinical evaluation. Pharmacotherapy 1989; 9 (1): 2–9.PubMed
51.
Plezia PM, Linford J, Kramer TH, et al. Transdermally administered fentanyl for postoperative pain: a randomized, doubleblind, placebo controlled trial [abstract]. Anesthesiology 1988; 69 (3A): A364.CrossRef
52.
Rowbotham DJ, Wyld R, Peacock JE, et al. Transdermal fentanyl for the relief of pain after upper abdominal surgery. Br J Anaesth 1989; 63 (1): 56–9.PubMedCrossRef
53.
Sandier AN, Baxter AD, Katz J, et al. A double-blind, placebocontrolled trial of transdermal fentanyl after abdominal hysterectomy: analgesic, respiratory, and pharmacokinetic effects [abstract 26]. Anesthesiology 1994; 81 (5): 1169–80.CrossRef
54.
Thompson JP, Bower S, Liddle AM, et al. Perioperative pharmacokinetics of transdermal fentanyl in elderly and young adult patients. Br J Anaesth 1998; 81: 152–4.PubMedCrossRef
55.
van Bastelaere M, Roily G, Abdullah NM. Postoperative analgesia and plasma levels after transdermal fentanyl for orthopedic surgery: double-blind comparison with placebo. J Clin Anesth 1995; 7 (1): 26–30.PubMedCrossRef
56.
van Bastelaere M, Roily G, van Peer A. Pharmacokinetic behaviour of transdermal fentanyl [abstract]. Br J Anesth 1993; 70 Suppl. 1: 75.
57.
van Lersberghe C, Camu F, de Keersmaecker E, et al. Continuous administration of fentanyl for postoperative pain: a comparison of the epidural, intravenous, and transdermal routes. J Clin Anesth 1994; 6 (4): 308–14.PubMedCrossRef
58.
von Bormann B, Ratthey K, Schwetlick G, et al. Postoperative Schmerztherapie durch transdermales fentanyl. Anästhesiologie Intensivmedizin Notfallmedizin Schmerztherapie 1988; 23 (1): 3–8.CrossRef
59.
Gupta SK, Southam M, Gale R, et al. System functionality and physicochemical model of fentanyl transdermal system. J Pain Symptom Manage 1992; 7 (3 Suppl.): S17–26.PubMedCrossRef
60.
Southam MA. Transdermal fentanyl therapy: system design, pharmacokinetics and efficacy. Anticancer Drugs 1995; 3: 29–34.CrossRef
61.
von Bonnann B. Clinical experience. In: Lehmann KA, Zech D, editors. Transdermal fentanyl. Berlin: Springer, 1991: 141–8.
62.
Gourlay GK, Mather LE. Pharmacokinetics and pharmacodynamics. In: Lehmann KA, Zech D, editors. Transdermal fentanyl. Berlin: Springer, 1991: 119–40.CrossRef
63.
Marquardt KA, Tharratt RS, Musallam NA. Fentanyl remaining in a transdermal system following three days of continuous use. Ann Pharmacother 1995; 29 (10): 969–71.PubMed
64.
Newshan G. Heat-related toxicity with the fentanyl transdermal patch. J Pain Symptom Manage 1998; 16 (5): 277–8.PubMedCrossRef
65.
Rose PG, Macfee MS, Boswell MV. Fentanyl transdermal system overdose secondary to cutaneous hyperthermia. Anesth Analg 1993; 77 (2): 390–1.PubMed
66.
Brunsch-Radbruch A, Radbruch L, Steeden E, et al. Transdermales Fentanyl in der klinischen Praxis - eine Anwendungsbeobachtung. Schmerz 1997; 11 Suppl. 1: S53–4.
67.
Donner B, Zenz M, Strumpf M, et al. Long-term treatment of cancer pain with transdermal fentanyl. J Pain Symptom Manage 1998; 15 (3): 168–75.PubMedCrossRef
68.
Payne R. Transdermal fentanyl: suggested recommendations for clinical use. J Pain Symptom Manage 1992; 7 (3 Suppl.): S40–4.PubMedCrossRef
69.
Simmonds MA, Richenbacher J. Transdermal fentanyl: long-term analgesic studies. J Pain Symptom Manage 1992; 7 (3 Suppl.): S36–9.PubMedCrossRef
70.
Payne R. Experience with transdermal fentanyl in advanced cancer pain. Eur J Pain 1990; 11: 98–101.
71.
Simmonds MA, Payne R, Richenbacher J, et al. TTS (fentanyl) in the management of pain in patients with cancer [abstract]. Proc Am Soc Clin Oncol 1989; 8: 234.
72.
Herbst LH, Strause LG. Transdermal fentanyl use in hospice home-care patients with chronic cancer pain. J Pain Symptom Manage 1992; 7 (3 Suppl.): S54–7.PubMedCrossRef
73.
Levy MH, Rosen SM, Kedziera P. Transdermal fentanyl: seeding trial in patients with chronic cancer pain. J Pain Symptom Manage 1992; 7 (3 Suppl.): S48–50.PubMedCrossRef
74.
Patt RB, Hogan LA. Transdermal fentanyl for chronic cancer pain: detailed case reports and the influence of confounding factors. J Pain Symptom Manage 1992; 7 (3 Suppl.): S51–3.PubMedCrossRef
75.
Maves TJ, Barcellos WA. Management of cancer pain with transdermal fentanyl: phase IV trial, University of Iowa. J Pain Symptom Manage 1992; 7 (3 Suppl.): S58–62.PubMedCrossRef
76.
Slover R. Transdermal fentanyl: clinical trial at the University of Colorado Health Sciences Center. J Pain Symptom Manage 1992; 7 (3 Suppl.): S45–7.PubMedCrossRef
77.
Ahmedzai S, Allan E, Fallon M, et al. Transdermal fentanyl in cancer pain. J Drug Dev 1994; 6 (3): 93–7.
78.
Yeo W, Lam KK, Chan AT, et al. Transdermal fentanyl for severe cancer-related pain. Palliat Med 1997; 11 (3): 233–9.PubMedCrossRef
79.
Wong JO, Chiu GL, Tsao CJ, et al. Comparison of oral controlled-release morphine with transdermal fentanyl in terminal cancer pain. Acta Anaesthesiol Sin 1997; 35 (1): 25–32.PubMed
80.
Hanks GW, Fallon MT. Transdermal fentanyl in cancer pain: conversion from oral morphine [letter; comment]. J Pain Symptom Manage 1995; 10 (2): 87.PubMedCrossRef
81.
Simmonds MA. Transdermal fentanyl: clinical development in the United States. Anticancer Drugs 1995; 3: 35–8.CrossRef
82.
Cote D. Dosage of transdermal fentanyl [letter; comment]. Clin Pharm 1993; 12 (10): 718.PubMed
83.
Kaiko RF. Use of transdermal fentanyl for cancer pain management [letter; comment]. Am Fam Physician 1993; 47 (4): 729–30.PubMed
84.
85.
Storey P. More on the conversion of transdermal fentanyl to morphine [letter; comment]. J Pain Symptom Manage 1995; 10 (8): 581–2.PubMedCrossRef
86.
Donner B, Zenz M, Tryba M, et al. Direct conversion from oral morphine to transdermal fentanyl: a multicenter study in patients with cancer pain. Pain 1996; 64 (3): 527–34.PubMedCrossRef
87.
Kulbe C, Radbruch L, Loick G, et al. Obstipation und Lax-antiengebrauch unter transdermalem Fentanyl im Vergleich zu oralem Morphin [abstract]. Schmerz 1997; 11 Suppl. 1: S54.
88.
Jage J, Portenoy RK, Foley KM. Die Bestimmung des i.m. Morphin Äquivalenz zur Therapie des Krebsschmerzes mit verschiedenen Opioiden oder beim Wechsel des Verabreichungsweges. Schmerz 1990; 4: 110–7.
89.
Miser AW, Narang PK, Dothage JA, et al. Transdermal fentanyl for pain control in patients with cancer. Pain 1989; 37 (1): 15–21.PubMedCrossRef
90.
Fudin J, Toledo-Binette C, Kupiak DM, et al. Quicker dosage adjustment for transdermal fentanyl. Am J Health Syst Pharm 1997; 54 (1): 87–8.PubMed
91.
Zech DF, Grond SU, Lynch J, et al. Transdermal fentanyl and initial dose-finding with patient-controlled analgesia in cancer pain: a pilot study with 20 terminally ill cancer patients. Pain 1992; 50 (3): 293–301.PubMedCrossRef
92.
Christie JM, Simmonds M, Patt R, et al. Dose titration, multicenter study of oral transmucosal fentanyl citrate for the treatment of breakthrough pain in cancer patients using transdermal fentanyl for persistent pain. J Clin Oncol 1998; 16 (10): 3238–45.PubMed
93.
Farrar JT, Cleary J, Rauck R, et al. Oral transmucosal fentanyl citrate: a randomized, double-blind, placebo-controlled trial for the treatment of breakthrough pain in cancer patients. J Natl Cancer Inst 1998; 90: 611–6.PubMedCrossRef
94.
Fine PG, Marcus M, De Boer AT, et al. An open label study of oral transmucosal fentanyl citrate (OTFC) for the treatment of breakthrough cancer pain. Pain 1991; 45: 149–55.PubMedCrossRef
95.
Portenoy RK, Payne R, Coluzzi P, et al. Oral transmucosal fentanyl citrate (OTFC) for the treatment of breakthrough pain in cancer patients: a controlled dose titration study. Pain 1999; 79: 303–12.PubMedCrossRef
96.
Korte W, Morant R. Transdermal fentanyl in uncontrolled cancer pain: titration on a day-to-day basis as a procedure for safe and effective dose finding — a pilot study in 20 patients. Support Care Cancer 1994; 2 (2): 123–7.PubMedCrossRef
97.
Korte W, de Stoutz N, Morant R. Day-to-day titration to initiate transdermal fentanyl in patients with cancer pain: short- and long-term experiences in a prospective study of 39 patients. J Pain Symptom Manage 1996; 11 (3): 139–46.PubMedCrossRef
98.
Brooks D. Day-to-day titration of transdermal fentanyl is unwise [letter; comment]. Support Care Cancer 1995; 3 (3): 210–1.PubMedCrossRef
99.
Hammack JE, Mailliard JA, Loprinzi CL, et al. Transdermal fentanyl in the management of cancer pain in ambulatory patients: an open-label pilot study. J Pain Symptom Manage 1996; 12 (4): 234–40.PubMedCrossRef
100.
Donner B, Zenz M, Tryba M, et al. Fentanyl TTS zur postoperativen Schmerztherapie. A neue Alternative? Anaesthesist 1993; 42 (5): 309–15.
101.
Billow HH, Linnemann M, Berg H, et al. Respiratory changes during treatment of postoperative pain with high dose trans-dermal fentanyl. Acta Anaesthesiol Scand 1995; 39 (6): 835–9.CrossRef
102.
Kilbride M, Morse M, Senagore A. Transdermal fentanyl improves management of postoperative hemorrhoidectomy pain. Dis Colon Rectum 1994; 37 (11): 1070–2.PubMedCrossRef
103.
Lehmann KA, Einnolf C, Eberlein HJ, et al. Transdermal fentanyl for the treatment of pain after major urological operations: a randomized double-blind comparison with placebo using intravenous patient-controlled analgesia. Eur J Clin Pharmacol 1991; 41 (1): 17–21.PubMedCrossRef
104.
Sevarino FB, Naulty JS, Sinatra R, et al. Transdermal fentanyl for postoperative pain management in patients recovering from abdominal gynecologic surgery. Anesthesiology 1992; 77 (3): 463–6.PubMedCrossRef
105.
Sevarino FB, Paige D, Sinatra RS, et al. Postoperative analgesia with parenteral opioids: does continuous delivery utilizing a transdermal opioid preparation affect analgesic efficacy or patient safety? J Clin Anesth 1997; 9 (3): 173–8.PubMedCrossRef
106.
Food and Drug Administration. Fentanyl transdermal system approved for chronic pain. JAMA 1990; 264: 1802.CrossRef
107.
Bernstein KZ, Klausner MA. Potential dangers related to transdermal fentanyl (Duragesic) when used for postoperative pain [letter; comment]. Dis Colon Rectum 1994; 37 (12): 1339–40.PubMedCrossRef
108.
Bernstein KJ. Inappropriate use of transdermal fentanyl for acute postoperative pain [letter]. J Oral Maxillofac Surg 1994; 52 (8): 896.PubMedCrossRef
109.
Press A. Women sues over painkiller patch. Persxx Times 1993 Nov 15: 4B.
110.
Vecchione A. Fentanyl linked to patient death in Nevada hospital. Hospital Pharmacist Report 1995; 12: 11.
111.
World Health Organization. Cancer Pain Relief. 2nd ed. Geneva: World Health Organization, 1996.
112.
Ventafridda V, Tamburini M, Caraceni A, et al. A validation study of the WHO method for cancer pain relief. Cancer 1987; 59 (4): 850–6.PubMedCrossRef
113.
Zech DF, Grond S, Lynch J, et al. Validation of World Health Organization guidelines for cancer pain relief: a 10-year prospective study. Pain 1995; 63 (1): 65–76.PubMedCrossRef
114.
Hardy JR, Rees AJ. A survey of transdermal fentanyl use in a major cancer center. J Pain Symptom Manage 1998; 15 (4): 213–4.PubMedCrossRef
115.
Leelanuntakit S. Management of cancer-related pain with transdermal fentanyl. J Med Assoc Thai 1996; 79 (6): 341–6.PubMed
116.
Slappendel R, Lako SJ, Crul BJP. Gastrointestinal side effects diminishes after switch over from morphine to transdermal fentanyl [abstract]. Ann Oncol 1994; 5 (Suppl. 8): S200.
117.
Sloan PA, Mouli DE, Hays H. Aclinical evaluation of transdermal therapeutic system fentanyl for the treatment of cancer pain. J Pain Symptom Manage 1998; 16: 102–111.PubMedCrossRef
118.
Megens AA, Artois K, Vermeire J, et al. Comparison of the analgesic and intestinal effects of fentanyl and morphine in rats. J Pain Symptom Manage 1998; 15 (4): 253–8.PubMedCrossRef
119.
Calis KA, Kohler DR, Corso DM. Transdermally administered fentanyl for pain management. Clin Pharm 1992; 11 (1): 22–36.PubMed
120.
Stoukides CA, Stegman M. Diffuse rash associated with transdermal fentanyl [letter]. Clin Pharm 1992; 11 (3): 222.PubMed
121.
Ahmedzai S, Brooks D. Transdermal fentanyl versus sustainedrelease oral morphine in cancer pain: preference, efficacy, and quality of life. The TTS-Fentanyl Comparative Trial Group. J Pain Symptom Manage 1997; 13 (5): 254–61.PubMedCrossRef
122.
Allan L, Hays H, Jensen NH, et al. Evidence for better analgesia with transdermal fentanyl in chronic pain treatment: comparison with sustained release morphine in a cross-over efficacy, safety and quality of life trial [abstract]. Anästhesiologie Intensivmedizin Notfallmedizin Schmerztherapie 1998; 33 (3 Suppl.): S435.
123.
Levy S, Jacobs S, Johnson J, et al. Transdermal fentanyl: pain and quality of life effects [abstract]. Proc Am Soc Clin Oncol 1988; 7: 292.
124.
Payne R, Matthias SD, Pasta DJ, et al. Quality of life in cancer pain: satisfaction and side effects with transdermal fentanyl versus oral morphine. J Clin Oncol 1998; 16: 1588–93.PubMed
125.
Kongsgaard UE, Poulain P. Transdermal fentanyl for pain control in adults with chronic cancer pain. Eur J Pain 1998; 2: 53–62.PubMedCrossRef
126.
Hardwick Jr WE, King WD, Palmisano PA. Respiratory depression in a child unintentionally exposed to transdermal fentanyl patch. South Med J 1997; 90 (9): 962–4.PubMedCrossRef
127.
Flannagan LM, Butts JD, Anderson WH. Fentanyl patches left on dead bodies: potential source of drug for abusers. J Forensic Sci 1996; 41 (2): 320–1.PubMed
128.
Edinboro LE, Poklis A, Trautman D, et al. Fatal fentanyl intoxication following excessive transdermal application. J Forensic Sci 1997; 42 (4): 741–3.PubMed
129.
Kramer C, Tawney M. Afatal overdose of transdermally administered fentanyl. J Am Osteopath Ass 1998; 98 (7): 385–6.PubMed
130.
De Sio JM, Bacon DR, Peer G, et al. Intravenous abuse of transdermal fentanyl therapy in a chronic pain patient. Anesthesiology 1993; 79 (5): 1139–41.CrossRef
131.
Marquardt KA, Tharratt RS. Inhalation abuse of fentanyl patch. Clin Toxicol 1994; 32 (1): 75–8.CrossRef
132.
Klockgether-Radke A, Hildebrandt J. Opioidintoxikation. Unsachgemäβe Anwendung von transdermalem Fentanyl. Anaesthesist 1997; 46 (5): 428–9.PubMedCrossRef
133.
Kuzma PJ, Kline MD, Stamatos JM, et al. Acute toxic delirium: an uncommon reaction to transdermal fentanyl. Anesthesiology 1995; 83 (4): 869–71.PubMedCrossRef
134.
Steinberg RB, Gilman DE, Johnson Fd. Acute toxic delirium in a patient using transdermal fentanyl. Anesth Analg 1992; 75 (6): 1014–6.PubMedCrossRef
135.
Link J. After transdermal fentanyl: acute toxic delirium or central anticholinergic syndrome? [letter; comment]. Anesthesiology 1996; 85 (2): 436–7.PubMedCrossRef
136.
Davies AN, Bond C. Transdermal fentanyl and the opioid withdrawal syndrome [letter]. Palliat Med 1996; 10 (4): 348.PubMed
137.
Higgs CM, Vella-Brincat J. Withdrawal with transdermal fentanyl [letter; comment]. J Pain Symptom Manage 1995; 10 (1): 4–5.PubMedCrossRef
138.
Zenz M, Donner B, Strumpf M. Withdrawal symptoms during therapy with transdermal fentanyl (fentanyl TTS)? J Pain Symptom Manage 1994; 9 (1): 54–5.PubMedCrossRef
139.
Portenoy RK. Opioid therapy for chronic nonmalignant pain: a review of the critical issues. J Pain Symptom Manage 1996; 11 (4): 203–17.PubMedCrossRef
140.
Dertwinkel R, Wiebalck A, Zenz M, et al. Orale Opioide zur Langzeittherapie chronischer Nicht-Tumorschmerzen. Anaesthesist 1996; 45 (6): 495–505.PubMedCrossRef
141.
Dellemijn PLI, van Duijn H, Vanneste JAL. Prolonged treatment with transdermal fentanyl in neuropathic pain. J Pain Symptom Manage 1998; 16: 220–9.PubMedCrossRef
142.
Simpson Jr RK, Edmondson EA, Constant CF, et al. Transdermal fentanyl as treatment for chronic low back pain. J Pain Symptom Manage 1997; 14 (4): 218–24.PubMedCrossRef
143.
Reinhart DJ, Goldberg ME, Roth JV, et al. Transdermal fentanyl system plus im ketorolac for the treatment of postoperative pain. Can J Anaesth 1997; 44 (4): 377–84.PubMedCrossRef
144.
Miguel R, Kreitzer JM, Reinhart D, et al. Postoperative pain control with a new transdermal fentanyl delivery system. A multicenter trial. Anesthesiology 1995; 83 (3): 470–7.PubMedCrossRef
145.
Holdsworth MT, Forman WB, Killilea TA, et al. Transdermal fentanyl disposition in elderly subjects. Gerontology 1994; 40 (1): 32–7.PubMedCrossRef
146.
Fiset P, Cohane C, Browne S, et al. Biopharmaceutics of a new transdermal fentanyl device. Anesthesiology 1995; 83 (3): 459–69.PubMedCrossRef
147.
Boerner TF, Bartkowski R, Torjman M, et al. Transdermal fentanyl: postoperative analgesia and plasma levels after major orthopedic surgery [abstract]. Anesth Analg 1992; 74 Suppl.: S31.
148.
Cigada M, Lenzi V, Sherif Afifi M, et al. Postoperative pain control by transdermal fentanyl: preliminary comparison of two dosages to a fixed-interval i.m. morphine regimen. Minerva Anestesiol 1992; 58 (12): 1323–30.PubMed
149.
Freedman G, Kreitzer J, Atlin N, et al. A new fentanyl transdermal delivery system: evaluation for pain relief following gynecologic surgery [abstract]. Anesthesiology 1991; 75 (3A): A708.CrossRef
150.
Lehmann LJ, De Sio JM, Radvany T, et al. Transdermal fentanyl in postoperative pain. Reg Anesth 1997; 22 (1): 24–8.PubMedCrossRef
151.
Stinchcomb AL, Paliwal A, Dua R, et al. Permeation of buprenorphine and its 3-alkyl-ester prodrugs through human skin. Pharm Res 1996; 13 (10): 1519–23.PubMedCrossRef
152.
Westerling D, Hoglund P, Lundin S, et al. Transdermal administration of morphine to healthy subjects. Br J Clin Pharmacol 1994; 37 (6): 571–6.PubMedCrossRef
153.
Ashburn MA, Streisand J, Zhang J, et al. The iontophoresis of fentanyl citrate in humans. Anesthesiology 1995; 82 (5): 1146–53.PubMedCrossRef
154.
155.
Vanbever R, Le Boulenge E, Preat V. Transdermal delivery of fentanyl by electroporation: I. Influence of electrical factors. Pharm Res 1996; 13 (4): 559–65.PubMedCrossRef
156.
Vanbever R, Morre ND, Preat V. Transdermal delivery of fentanyl by electroporation: II. Mechanisms involved in drug transport. Pharm Res 1996; 13 (9): 1360–6.PubMedCrossRef
157.
Stephen R, Miotti D, Bettaglio R, et al. Electromotive administration of a new morphine formulation: morphine citrate. Artif Organs 1994; 18 (6): 461–5.PubMedCrossRef
158.
Ashburn MA, Stephen RL, Ackerman E, et al. Iontophoretic delivery of morphine for postoperative analgesia. J Pain Symptom Manage 1992; 7 (1): 27–33.PubMedCrossRef
159.
Thysman S, Tasset C, Preat V. Transdermal iontophoresis of fentanyl: delivery and mechanistic analysis. Int J Pharm 1994; 101: 105–13.CrossRef
160.
Thysman S, Preat V. In vivo iontophoresis of fentanyl and sufentanil in rats: pharmacokinetics and acute antinociceptive effects. Anesth Analg 1993; 77 (1): 61–6.PubMedCrossRef
161.
Gupta SK, Southam M, Woestenborghs R, et al. On-demand fentanyl delivery from an electrotransport therapeutic system (ETS): consistent drug delivery independent of bolus frequency. 8th World Congress on Pain; 1996 Aug 17–22; Vancouver (BC). 163.
162.
Gupta SK, Southam M, Sathyan G, et al. Effect of current density on pharmacokinetics following continuous or intermittent input from a fentanyl electrotransport system. J Pharm Sci 1998; 87 (8): 976–81.PubMedCrossRef
163.
Gupta SK, Bernstein KJ, Noorduin H, et al. Fentanyl delivery from an electrotransport system: delivery is a function of total current, not duration of current. J Clin Pharmacol 1998; 38: 951–8.PubMed
164.
Dunn C. ‘Touch of a button’ delivers transdermal fentanyl. Inpharma 1997; 1087: 19–20.CrossRef
Metadata
Title
Clinical Pharmacokinetics of Transdermal Opioids
Focus on Transdermal Fentanyl
Authors
Dr Stefan Grond
Lukas Radbruch
Klaus A. Lehmann
Publication date
01-01-2000
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 1/2000
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.2165/00003088-200038010-00004