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Noninvasive drug delivery

Abstract

Advances in biopharmaceutical technology have spawned new drug delivery devices and mechanisms. Noninvasive methods, including iontophoresis and transmucosal drug delivery, have improved treatment of certain patient population. Their use is discussed in the following paper.

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References

  1. 1.

    Elias PM, Protective role of the skin: the special role of the stratum corneum. In: Fitzpatrick, TB, ed, Dermatology in Medicine, New York: McGraw-Hill, 1987:213

    Google Scholar 

  2. 2.

    Guy, RH, Hadgraft, J, Bucks DAW. Transdermal drug delivery and cutaneous metabolism. Xenobiotica. 1987;17:325–343.

    PubMed  CAS  Article  Google Scholar 

  3. 3.

    Hertzmann AB, Randall WC. Regional differences in the basal and maximal rates of blood flow in the skin. J Appl Physiol. 1948;1:234–241.

    Google Scholar 

  4. 4.

    Duthrie DJR, Rowbotham DJ, Wyld R, Henderson PD, Nimmo WS. Plasma fentanyl concentrations during transdermal delivery of fentanyl to surgical patients. Br J Anaesth. 1988;60:614–618.

    Article  Google Scholar 

  5. 5.

    Holley FO, Van Steenis C. Postoperative analgesia with fentanyl: pharmacokinetics and pharmacodynamics of constant-rate iv and transdermal delivery. Br J Anaesth. 1988;60:608–613.

    PubMed  Article  CAS  Google Scholar 

  6. 6.

    Portnoy R, Southam M, Gupta S, et al. Transdermal fentanyl for cancer pain. Repeated dose pharmacokinetics. Anesthesiology. 1993;78:36–43.

    Article  Google Scholar 

  7. 7.

    Varvel JR, Shafer SL, Hwang SS, Coen PA, Stanski DR. Absorption characteristics of transdermally administered fentanyl. Anesthesiology. 1989;70:928–934.

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Sandler A, Baxter A, Katz J, et al. A double-blind, placebo-controlled, trial of transdermal fentanyl after abdominal hysterectomy. Anesthesiology. 1994;81:1169–1179.

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Portnoy R, Hagen N. Breakthrough pain: definition, prevalence and characteristics. Pain. 1990;41:273–281.

    Article  Google Scholar 

  10. 10.

    Fiset P, Cohane C, Browne S, Brand S, Shafer S. Biopharmaceutics of a new transdermal fentanyl device. Anesthesiology 1995;83:459–469.

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Miguel R, Kreitzer J, Reinhart D, et al. Postoperative pain control with a new transdermal fentanyl delivery system. Anesthesiology. 1995;83:470–477.

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Shomaker TS, Ashburn MA. The assessment of the impact of heat on the systemic delivery of fentanyl through the transdermal fentanyl delivery system. Pain Med. 2000;1:193–194.

    Google Scholar 

  13. 13.

    Soliman I, Broadman L, Hannallah S, McGill W. Comparison of the analgesic effects of EMLA (eutectic mixture of local anesthetics) to intradermal lidocaine infiltration prior to venous cannulation in unpremedicated children. Anesthesiology. 1988;68:804–806.

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Ogborn M. The use of a eutectic mixture of local anesthetic in pediatric renal biopsy. Pediatr Nephrol. 1992;6:276–277.

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Lycka B. EMLA: A new and effective topical anesthetic. J Dermatol Surg Oncol. 1992;18:859–862.

    PubMed  CAS  Google Scholar 

  16. 16.

    Benini F, Johnston C, Faucher D, Aranda JV. Topical anesthesia during circumcision in newborn infants. JAMA. 1993;270:850–853.

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Hallen B, Olsson G, Uppfeldt A. Pain-free venepuncture. Effect of timing of application of local anaesthetic cream. Anaesthesia. 1984;39:969–972.

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    Malmros I, Nelsen T, Lillieborg S. Plasma concentrations and analgesic effect of EMLA (lidocaine/prilocaine) cream for the cleansing of leg ulcers. Acta Derm Venereol (Stockh). 1990;70:227–230.

    Google Scholar 

  19. 19.

    Ashburn MA, Love G, Zhang J, Basta J, Stanley TH. Determination of the depth and duration of skin anesthesia using an S-Caine® drug delivery system in normal healthy adults [Abstract]. Anesthesiology 1998;89:A893.

    Article  Google Scholar 

  20. 20.

    Bezzant JL, Pentelenz TJ, Jacobsen SC. Painless cauterization of spider veins using iontophoretic local anesthesia. J Am Acad Dermatol. 1988;19:869–875.

    PubMed  CAS  Google Scholar 

  21. 21.

    Harris PR. Iontophoresis: clinical research in musculoskeletal inflammatory conditions. JOSPT. 1982;4:109–112.

    PubMed  CAS  Google Scholar 

  22. 22.

    Sloan JB, Soltani K. Iontophoresis in dermatology. J Am Acad Dermatol. 1986;15:671–684.

    PubMed  CAS  Google Scholar 

  23. 23.

    Ashburn MA, Stephen RL, Ackerman E, et al. Iontophoretic delivery of morphine for postoperative analgesia. J Pain Symptom Manag. 1991;7:27–33.

    Article  Google Scholar 

  24. 24.

    Ashburn M, Streisand J, Zhang J, et al. The iontophoresis of fentanyl citrate in humans. Anesthesiology. 1995;82:1146–1153.

    PubMed  Article  CAS  Google Scholar 

  25. 25.

    Glass JM, Stephen RL, Jacobson SC. The quantity and distribution of radiolabeled dexamethasone delivered to tissue by iontophoresis. Int J Derm. 1980;19:519–525.

    PubMed  CAS  Google Scholar 

  26. 26.

    Hasson SH, Henderson GH, Daniels JC, Schieb DA. Exercise training and dexamethasone iontophoresis in rheumatoid arthritis: a case study. Physiother Can. 1991;43:11–14.

    Google Scholar 

  27. 27.

    Davis WT, Jr.. Use of iontophoresis for oral mucosal anesthesia. SC Dent J. 1981;39:53–57.

    CAS  Google Scholar 

  28. 28.

    Kennard CD, Whitaker DC. Iontophoresis of lidocaine for anesthesia during pulsed due laser treatment of port-wine stains. J Dermatol Surg Oncol. 1992;18:287–294.

    PubMed  CAS  Google Scholar 

  29. 29.

    Sisler HA. Iontophoretic local anesthesia for conjuctival surgery. Ann Ophthalmol. 1978;10:597–598.

    PubMed  CAS  Google Scholar 

  30. 30.

    Ashburn M, Gauthier M, Love G, Basta S, Gaylord B, Kessler K. Iontophoretic administration of 2% lidocaine HCl and 1∶100,000 epinephrine in humans. Clin J Pain. 1997;13:22–26.

    PubMed  Article  CAS  Google Scholar 

  31. 31.

    Petelenz TJ. Selected topics in iontophoresis. University of Utah, 1989.

  32. 32.

    Ashburn MA, Streisand JB, Zhang J, et al. The iontophoresis of fentanyl citrate in humans. Anesthesiology. 1995;87:1146–1153.

    Article  Google Scholar 

  33. 33.

    McClain DA, Hug CC. Intravenous fentanyl kinetics. Clin Pharmacol. Ther. 1980;28:106–114.

    PubMed  CAS  Article  Google Scholar 

  34. 34.

    Gibaidi M, Kanig J. Absorption of drugs through the oral mucosa. J Oral Ther Pharmacol. 1965;1:440–450.

    Google Scholar 

  35. 35.

    Weinberg DS, Inturrisi CE, Reidenberg B, et al. Sublingual absorption of selected opioid analgesics. Clin Pharmacol Ther. 1988;44:335–342.

    PubMed  CAS  Article  Google Scholar 

  36. 36.

    Gordon GS, Moses AC, Silver RD, Flier JS, Carey MC. Nasal absorption on insulin: enhancement by hydrophobic bile salts. Proc Natl Acad Sci USA 1985;82:7419.

    PubMed  Article  CAS  Google Scholar 

  37. 37.

    Streisand J, Zhang J, Niu S, McJames S, Natte R, Pace N. Buccal absorption of fentanyl is pH-dependent in dogs. Anesthesiology. 1995;82:759–764.

    PubMed  CAS  Article  Google Scholar 

  38. 38.

    Al-Sayed-Omar O, Johnston A, Turner P. Influence of pH on the buccal absorption of morphine sulphate and its major metabolite, morphine-3-glucuronide. J Pharm Pharmacol 1987;39:934–935.

    PubMed  CAS  Google Scholar 

  39. 39.

    Manara AR, Shelly MP, Quinn KG, Park GR. Pharmacokinetics of morphine following administration by the buccal route. Br J Anaesth. 1989;62:498–502.

    PubMed  Article  CAS  Google Scholar 

  40. 40.

    Fisher AP, Fung C, Hanna M. Serum morphine concentrations after buccal and intramuscular morphine administration. Br J Clin Pharmacol. 1978;24:685–687.

    Google Scholar 

  41. 41.

    Fisher AP, Fung C, Hanna M. Absorption of buccal morphine. Anaesthesia. 1988;43:552–553.

    PubMed  Article  CAS  Google Scholar 

  42. 42.

    Hoskin PJ, Hanks GW, Aherne GW, Chapman D, Littleton P, Filshie J. The bioavailability and pharmacokinetics of morphine after intravenous, oral and buccal administration in healthy volunteers. Br J Clin Pharmacol. 1989;27:499–505.

    PubMed  CAS  Google Scholar 

  43. 43.

    Shepard KV, Bakst AW. Alternate delivery methods for morphine sulfate in cancer pain. Cleve Clin J Med. 1990;57:48–52.

    PubMed  CAS  Google Scholar 

  44. 44.

    Pannuti F, Rossi AP, Iafelice G, et al. Control of chronic pain in very advanced cancer patients with morphine hydrochloride administered by oral, rectal and sublingual route. Clinical report and preliminary results on morphine pharmacokinetics. Pharmacol Res Commun. 1982;14:369–380.

    PubMed  Article  CAS  Google Scholar 

  45. 45.

    Bell MDD, Mishra P, Weldon BD, Murray GR, Calvey TN, Williams NE. Buccal morphine—new route for analgesia? Lancet. 1985;1:71–73.

    PubMed  Article  CAS  Google Scholar 

  46. 46.

    Maunuksela E-L, Korpela R, Oikkola KT. Comparison of buprenorphine with morphine in the treatment of postoperative pain in children. Anesth Analg. 1988;67:233–239.

    PubMed  Article  CAS  Google Scholar 

  47. 47.

    Wallenstein S, Kaiko R, Rogers A. Crossover trials in clinical analgesic assays: studies of buprenorphine and morphine. Pharmacotherapy 1986;6:228–235.

    PubMed  CAS  Google Scholar 

  48. 48.

    Bullingham RES, McQuay HJ, Porter EJB, Allen MC. Sublingual buprenorphine used postoperatively: ten hour plasma drug concentration analysis. Br J Clin Pharmacol. 1982;13:665–673.

    PubMed  CAS  Google Scholar 

  49. 49.

    Bullingham RES, McQuay HJ, Dwyer D, Allen MC, Moore RA. Sublingual buprenorphine used postoperatively: Clinical observations and preliminary pharmacokinetic analysis. Br J Clin Pharmacol. 1981;12:117–122.

    PubMed  CAS  Google Scholar 

  50. 50.

    O'Sullivan G, Bullingham R, McQuay H, et al. A comparison of intramuscular and sublingual buprenorphine intramuscular morphine, and placebo as premedication. Anaesthesia. 1983;38:977–984.

    PubMed  Article  Google Scholar 

  51. 51.

    Korttila K, Hovorka J. Buprenorphine as premedication and as analgesic during and after light isoflurane-N2O-O2 anaesthesia: a comparison with oxycodone plus fentanyl. Acta Anaesthesiol Scand. 1987;31:673–679.

    PubMed  CAS  Google Scholar 

  52. 52.

    Streisand J, Varvel J, Stanski D, et al. Absorption and bioavailability of oral transmucosal fentanyl citrate. Anesthesiology 1991;75:223–229.

    PubMed  Article  CAS  Google Scholar 

  53. 53.

    Gourlay GK, Kowalski SR, Plummer JL, Cousins MJ. Armstrong PJ. Fentanyl blood concentration-analgesic response relationship in treatment of postoperative pain. Anesth Analg. 1988;67:329–337.

    PubMed  Article  CAS  Google Scholar 

  54. 54.

    Schechter N, Weisman S, Rosenblum M, Bernstein B, Conard P. The use of oral transmucosal fentanyl citrate for painful procedures in children. Pediatrics 1995;95:335–339.

    PubMed  CAS  Google Scholar 

  55. 55.

    Schutzman S, Burg J, Liebelt E, et al. Oral transmucosal fentanyl citrate for premedication of children undergoing laceration repair. Ann Emerg Med. 1994;24:1059–1064.

    PubMed  Article  CAS  Google Scholar 

  56. 56.

    Gerwels J, Bezzant J, LeMaire L, Pauley L, Streisand J. Oral transmucosal fentanyl citrate premedication in patients undergoing outpatient dermatologic procedures. J Dermatol Surg Oncol. 1994;20:823–826.

    PubMed  CAS  Google Scholar 

  57. 57.

    Epstein R, Mendel H, Witkowski T, et al Preop sedation with Oralet in 2 to 6 year old children [Abstract]. Anesthesiology 1995;83:Al179.

    Google Scholar 

  58. 58.

    Ashburn MA, Streisand JB, Tarver SD, et al. Oral transmucosal fentanyl citrate for premedication in paediatric outpatients. Can J Anaesth. 1990;37:857–866.

    PubMed  CAS  Article  Google Scholar 

  59. 59.

    Fine PG, Marcus M, De Boer JA, Van der Oord B: An open label study of oral transmucosal fentanyl citrate (OTFC) for the treatment of breakthrough cancer pain. Pain. 1991;45:149–153.

    PubMed  Article  CAS  Google Scholar 

  60. 60.

    Shyu W, Pittman K, Robinson D. The absolute bioavailability of transnasal butorphanol in patients experiencing rhinitis. Eur J Clin Pharmacol. 1993;45:559–562.

    PubMed  Article  CAS  Google Scholar 

  61. 61.

    Abboud T, Zhu J, Gangolly J, et al. Transnasal butorphanol: a new method for pain relief in postcesarian section pain. Acta Anaesthesiol Scand. 1991;35:14–18.

    PubMed  CAS  Google Scholar 

  62. 62.

    Baumel B. Migraine: a pharmacologic review with newer options and delivery modalities. Neurology 1994;44(Suppl 13):S13-S17.

    PubMed  CAS  Google Scholar 

  63. 63.

    Abboud T, Zhu J, Longhitano M, et al. Efficacy and safety of butorphanol nasal spray for the relief of postepisiotomy pain. Curr Ther Res. 1994;55:500–509.

    Article  Google Scholar 

  64. 64.

    Tobias J, Rasmussen G. Transnasal butorphanol for postoperative analgesia following paediatric surgery in a third world country. Paediatr Anaesth. 1995;5:63–66.

    PubMed  Article  CAS  Google Scholar 

  65. 65.

    Scott W, Smith M, Sanford S. Effectiveness of transnasal butorphanol for the treatment of musculoskeletal pain. Am J Emerg Med. 1994;12:469–471.

    PubMed  Article  CAS  Google Scholar 

  66. 66.

    Striebel H, Koenigs D, Kramer J Postoperative pain management by intranasal demand-adapted fentanyl titration. Anesthesiology. 1992;77:281–285.

    PubMed  Article  CAS  Google Scholar 

  67. 67.

    Heimers JH, Noorduin H, Van Peer A, Van Leeuwen L, Zuurmond WWA. Comparison of intravenous and intranasal sufentanil absorption and sedation. Can J Anaesth. 1989;36:494–497.

    Article  Google Scholar 

  68. 68.

    Vercauteren M, Boeckx E, Hanegreefs G, Noorduin J, Vandenbussche G: Intranasal sufentanil for pre-operative sedation. Anaesthesia. 1988;43:270–273.

    PubMed  Article  CAS  Google Scholar 

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Correspondence to Ruth Zimmer MD.

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Zimmer, R., Ashburn, M.A. Noninvasive drug delivery. Compr Ther 27, 293–301 (2001). https://doi.org/10.1007/s12019-001-0027-z

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Keywords

  • Morphine
  • Fentanyl
  • Buprenorphine
  • Butorphanol
  • Comp THER