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Oral Mucosal Drug Delivery

Clinical Pharmacokinetics and Therapeutic Applications

Abstract

Oral mucosal drug delivery is an alternative method of systemic drug delivery that offers several advantages over both injectable and enteral methods. Because the oral mucosa is highly vascularised, drugs that are absorbed through the oral mucosa directly enter the systemic circulation, bypassing the gastrointestinal tract and first-pass metabolism in the liver. For some drugs, this results in rapid onset of action via a more comfortable and convenient delivery route than the intravenous route. Not all drugs, however, can be administered through the oral mucosa because of the characteristics of the oral mucosa and the physicochemical properties of the drug.

Several cardiovascular drugs administered transmucosally have been studied extensively. Nitroglycerin is one of the most common drugs delivered through the oral mucosa. Research on other cardiovascular drugs, such as captopril, verapamil and propafenone, has proven promising.

Oral transmucosal delivery of analgesics has received considerable attention. Oral transmucosal fentanyl is designed to deliver rapid analgesia for breakthrough pain, providing patients with a noninvasive, easy to use and nonintimidating option. For analgesics that are used to treat mild to moderate pain, rapid onset has relatively little benefit and oral mucosal delivery is a poor option.

Oral mucosal delivery of sedatives such as midazolam, triazolam and etomidate has shown favourable results with clinical advantages over other routes of administration. Oral mucosal delivery of the antinausea drugs scopolamine and prochlorperazine has received some attention, as has oral mucosal delivery of drugs for erectile dysfunction.

Oral transmucosal formulations of testosterone and estrogen have been developed. In clinical studies, sublingual testosterone has been shown to result in increases in lean muscle mass and muscle strength, improvement in positive mood parameters, and increases in genital responsiveness in women. Short-term administration of estrogen to menopausal women with cardiovascular disease has been shown to produce coronary and peripheral vasodilation, reduction of vascular resistance and improvement in endothelial function. Studies of sublingual administration of estrogen are needed to clarify the most beneficial regimen.

Although many drugs have been evaluated for oral transmucosal delivery, few are commercially available. The clinical need for oral transmucosal delivery of a drug must be high enough to offset the high costs associated with developing this type of product. Drugs considered for oral transmucosal delivery are limited to existing products, and until there is a change in the selection and development process for new drugs, candidates for oral transmucosal delivery will be limited.

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References

  1. 1.

    Sayani AP, Chien YW. Systemic delivery of peptides and proteins across absorptive mucosae. Crit Rev Ther Drug Carrier Syst 1996; 13: 85–184

    PubMed  CAS  Google Scholar 

  2. 2.

    Motwani JG, Lipworth BJ. Clinical pharmacokinetics of drugs administered buccally and sublingually. Clin Pharmacokinet 1991; 21(2): 83–94

    PubMed  CAS  Article  Google Scholar 

  3. 3.

    Squier CA, Wertz PW. Structure and function of the oral mucosa and implications for drug delivery. In: Rathbone MJ, editor. Oral mucosal drug delivery. New York: Marcel Dekker, Inc., 1996: 1–26

    Google Scholar 

  4. 4.

    Collins LMC, Dawes C. The surface area of the adult human mouth and thickness of the salivary film covering the teeth and oral mucosa. J Dent Res 1987; 66(8): 1300–2

    PubMed  CAS  Article  Google Scholar 

  5. 5.

    Squier CA, Wertz PW. Permeability and the pathophysiology of oral mucosa. Adv Drug Deliv Rev 1993; 12: 13–24

    Article  Google Scholar 

  6. 6.

    Jacob SW, Francone CA. Structure and function of man. Philadelphia (PA): WB Saunders Co., 1970

    Google Scholar 

  7. 7.

    Squier CA, Nanny D. Measurement of blood flow in the oral mucosa and skin of the Rhesus monkey using radiolabeled microspheres. Arch Oral Biol 1985; 30: 313–8

    PubMed  CAS  Article  Google Scholar 

  8. 8.

    Squier CA. The permeability of keratinized and nonkeratinized oral epithelium to horseradish peroxidase. J Ultrastruct Res 1973; 43: 160–77

    PubMed  CAS  Article  Google Scholar 

  9. 9.

    Squier CA, Rooney L. The permeability of keratinized and nonkeratinized oral epithelium to lanthanum in vivo. J Ultrastruc Res 1976; 54: 286–95

    CAS  Article  Google Scholar 

  10. 10.

    Dowty ME, Knuth KE, Irons BK, et al. Transport of thyrotropin releasing hormone in rabbit buccal mucosa in vitro. Pharm Res 1992; 9(9): 1113–22

    PubMed  CAS  Article  Google Scholar 

  11. 11.

    Squier CA, Johnson NW, Hackemann M. Structure and function of normal human oral mucosa. In: Dolby AE, editor. Oral mucosa in health and disease. Oxford: Blackwell Scientific Publications, 1975: 1–112

    Google Scholar 

  12. 12.

    Kirsten R, Nelson K, Kirsten D, et al. Clinical pharmacokinetics of vasodilators. Part II. Clin Pharmacokinet 1998 Jul; 35(1): 9–36

    PubMed  CAS  Article  Google Scholar 

  13. 13.

    Bogaert MG. Clinical pharmacokinetics of nitrates. Cardiovasc Drugs Ther 1994 Oct; 8: 693–9

    PubMed  CAS  Article  Google Scholar 

  14. 14.

    Hamilton RJ, Carter WA, Gallagher EJ. Rapid improvement of acute pulmonary edema with sublingual captopril. Acad Emerg Med 1996 Mar; 3(3): 205–12

    PubMed  CAS  Article  Google Scholar 

  15. 15.

    Al-Furaih TA, McElnay JC, Elborn JS, et al. Sublingual captopril: a pharmacokinetic and pharmacodynamic evaluation. Eur J Clin Pharmacol 1991; 40: 393–8

    PubMed  CAS  Article  Google Scholar 

  16. 16.

    McElnay JC, Al-Furaih TA, Hughes CM, et al. The effect of pH on the buccal and sublingual absorption of captopril. Eur J Clin Pharmacol 1995; 48: 373–9

    PubMed  CAS  Article  Google Scholar 

  17. 17.

    McElnay JC, Al-Furaih TA, Hughes CM, et al. A pharmacokinetic and pharmacodynamic evaluation of buffered sublingual captopril in patients with congestive heart failure. Eur J Clin Pharmacol 1996; 49: 471–6

    PubMed  CAS  Article  Google Scholar 

  18. 18.

    Asthana OP, Woodcock BG, Wenchel M, et al. Verapamil disposition and effect on PQ-intervals after buccal, oral and intravenous administration. Drug Res 1984; 34(1): 498–502

    CAS  Google Scholar 

  19. 19.

    John DN, Fort S, Lewis MJ, et al. Pharmacokinetics and pharmacodynamics of verapamil following sublingual and oral administration to healthy volunteers. Br J Clin Pharmacol 1992; 33: 623–7

    PubMed  CAS  Article  Google Scholar 

  20. 20.

    Fort S, Lewis MJ, Luscombe DK, et al. Preliminary investigation of the efficacy of sublingual verapamil in the management of acute atrial fibrillation and flutter. Br J Clin Pharmacol 1994; 37: 460–3

    PubMed  CAS  Article  Google Scholar 

  21. 21.

    Berk SI, Beckman K, Hoon TJ, et al. Comparison of the pharmacokinetics and electrocardiographic effects of sublingual and intravenous verapamil. Pharmacotherapy 1992; 12(1): 33–9

    PubMed  CAS  Google Scholar 

  22. 22.

    Al-Waili NS, Hasan NA. Efficacy of sublingual verapamil in patients with severe essential hypertension: comparison with sublingual nifedipine. Eur J Med Res 1999; 4: 193–8

    PubMed  CAS  Google Scholar 

  23. 23.

    Grossman E, Messerli FH, Grodzicki T, et al. Should a moratorium be placed on sublingual nifedipine capsules given for hypertensive emergencies and pseudoemergencies? J Am Med Assoc 1996; 276(16): 1328–31

    CAS  Article  Google Scholar 

  24. 24.

    Sasaki S, Koumi S, Sato R, et al. Kinetics of buccal absorption of propafenone single oral loading dose in healthy humans. Gen Pharmacol 1998; 31(4): 589–91

    PubMed  CAS  Article  Google Scholar 

  25. 25.

    Portenoy RK, Payne R, Coluzzi P, et al. Oral transmucosal fentanyl citrate (OTFC) for the treatment of breakthrough pain in cancerpatients: acontrolled dose titration study. Pain 1999; 79: 303–12

    PubMed  CAS  Article  Google Scholar 

  26. 26.

    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: 3238–45

    PubMed  CAS  Google Scholar 

  27. 27.

    Farrar JT, Cleary J, Rauck R, et al. Oral transmucosal fentanyl citrate: randomized, double-blinded, placebo-controlled trial for treatment of breakthrough pain in cancer patients. J Natl Cancer Inst 1998; 90: 611–6

    PubMed  CAS  Article  Google Scholar 

  28. 28.

    Streisand JB, Varvel JR, Stanski DR, et al. Absorption and bio-availability of oral transmucosal fentanyl citrate. Anesthesiology 1991; 75: 223–9

    PubMed  CAS  Article  Google Scholar 

  29. 29.

    Egan TD, Sharma A, Ashburn MA, et al. Multiple dose pharmacokinetics of oral transmucosal fentanyl citrate in healthy volunteers. Anesthesiology 2000; 92: 665–73

    PubMed  CAS  Article  Google Scholar 

  30. 30.

    Streisand JB, Busch MA, Egan TD, et al. Dose proportionality and pharmacokinetics of oral transmucosal fentanyl citrate. Anesthesiology 1998; 88: 305–9

    PubMed  CAS  Article  Google Scholar 

  31. 31.

    Lichtor JL, Sevarino FB, Joshi GP, et al. The relative potency of oral transmucosal fentanyl citrate (OTFC) compared with intravenous morphine in the treatment of moderate to severe postoperative pain. Anesth Anal 1999; 89(3): 732–8

    CAS  Google Scholar 

  32. 32.

    Coluzzi PH, Schwartzberg L, Conroy JD, et al. Breakthrough cancer pain: a randomized trial comparing oral transmucosal fentanyl citrate (OTFC®) and morphine sulfate immediate release (MSIR®). Pain 2001; 91: 123–30

    PubMed  CAS  Article  Google Scholar 

  33. 33.

    Coluzzi PH. Sublingual morphine: efficacy reviewed. J Pain Symptom Manage 1998 Sep; 16(3): 184–92

    PubMed  CAS  Article  Google Scholar 

  34. 34.

    Weinberg DS, Intanisi CE, Reidenberg B, et al. Sublingual absorption of selected opioid analgesics. Clin Pharmacol Ther 1988; 44: 335–42

    PubMed  CAS  Article  Google Scholar 

  35. 35.

    Davis T, Miser AW, Loprinzi CI, et al. Comparative morphine pharmacokinetics following sublingual, intramuscular, and oral administration in patients with cancer. Hospice 1993; 9: 85–90

    CAS  Article  Google Scholar 

  36. 36.

    Robison JM, Wilkie DJ, Campbell B. Sublingual and oral morphine administration. Nurs Clin North Am 1995; 30: 725–43

    PubMed  CAS  Google Scholar 

  37. 37.

    Watson NW, Taylor KMG, Joel SP, et al. A pharmacokinetic study of sublingual aerosolized morphine in healthy volunteers. J Pharm Pharmacol 1996; 48: 1256–9

    PubMed  CAS  Article  Google Scholar 

  38. 38.

    Chawarski MC, Schottenfeld RS, O’Connor PG, et al. Plasma concentrations of buprenorphine 24 to 72 hours after dosing. Drug Alcohol Depend 1999; 55: 157–63

    PubMed  CAS  Article  Google Scholar 

  39. 39.

    Walsh SL, Preston KL, Stitzer ML, et al. Clinical pharmacology of buprenorphine: ceiling effects at high doses. Clin Pharmacol Ther 1994 May; 55(5): 569–80

    PubMed  CAS  Article  Google Scholar 

  40. 40.

    Bullingham RES, McQuay HJ, Porter EJB, et al. Sublingual buprenorphine used postoperatively: ten hour plasma drug concentration analysis. Br J Clin Pharmacol 1982; 13: 665–73

    PubMed  CAS  Article  Google Scholar 

  41. 41.

    Kuhlman JJ, Lalani S, Magluilo J, et al. Human pharmacokinetics of intravenous, sublingual and buccal buprenorphine. J Anal Toxicol 1996 Oct; 20: 369–78

    PubMed  CAS  Google Scholar 

  42. 42.

    Mendelson J, Upton RA, Everhart ET, et al. Bioavailability of sublingual buprenorphine. J Clin Pharmacol 1997; 37: 31–7

    PubMed  CAS  Article  Google Scholar 

  43. 43.

    Nath RP, Upton RA, Everhart ET, et al. Buprenorphine pharmacokinetics: relative bioavailability of sublingual tablet and liquid formulations. J Clin Pharmacol 1999; 39: 619–23

    PubMed  CAS  Article  Google Scholar 

  44. 44.

    Schuh KJ, Johanson C. Pharmacokinetic comparison of the buprenorphine sublingual liquid and tablet. Drug Alcohol Depend 1999; 56: 55–60

    PubMed  CAS  Article  Google Scholar 

  45. 45.

    Shyu WC, Mayol RF, Pfeffer M, et al. Biopharmaceutical evaluation of transnasal, sublingual, and buccal disk dosage forms of butorphanol. Biopharm Drug Dispos 1993; 14: 371–9

    PubMed  CAS  Article  Google Scholar 

  46. 46.

    Nappi G, Micieli G, Tassorelli C, et al. Effectiveness of a piroxicam fast dissolving formulation sublingually administered in the symptomatic treatment of migraine without aura. Headache 1993; 33: 296–300

    PubMed  CAS  Article  Google Scholar 

  47. 47.

    Mueller BA, Rex DK, Figueroa N, et al. A pharmacokinetic and endoscopic comparison of an oral and an experimental buccal piroxicam formulation. Pharmacotherapy 1992; 12(2): 93–7

    PubMed  CAS  Google Scholar 

  48. 48.

    Yalçin S, Altundag K, Asil M, et al. Sublingual piroxicam for cancer pain. Med Oncol 1998; 15: 137–9

    PubMed  Article  Google Scholar 

  49. 49.

    Schwagmeier R, Alincic S, Striebel HW. Midazolam pharmacokinetics following intravenous and buccal administration. Br J Clin Pharmacol 1998; 46: 203–6

    PubMed  CAS  Article  Google Scholar 

  50. 50.

    Scott RC, Besag FMC, Boyd SG, et al. Buccal absorption of midazolam: pharmacokinetics and EEG pharmacodynamics. Epilepsia 1998; 39(3): 290–4

    PubMed  CAS  Article  Google Scholar 

  51. 51.

    Junko F, Nobuo I, Nakano M. Relative bioavailability of midazolam following sublingual versus oral administration in healthy volunteers. J Pharmacobiodyn 1988; 11: 206–9

    Article  Google Scholar 

  52. 52.

    Karl HW, Rosenberger JL, Larach MG, et al. Transmucosal administration of midazolam for premedication of pediatric patients. Anesthesiology 1993; 78(5): 885–91

    PubMed  CAS  Article  Google Scholar 

  53. 53.

    Geldner G, Hubmann M, Knoll R, et al. Comparison between three transmucosal routes of administration of midazolam in children. Paediatr Anaesth 1997; 7: 103–9

    PubMed  CAS  Article  Google Scholar 

  54. 54.

    Kroboth PD, McAuley JW, Kroboth FJ, et al. Triazolam pharmacokinetics after intravenous, oral, and sublingual administration. J Clin Psychopharmacol 1995; 15(4): 259–62

    PubMed  CAS  Article  Google Scholar 

  55. 55.

    Scavone JM, Greenblatt DJ, Friedman H, et al. Enhanced bioavailability of triazolam following sublingual versus oral administration. J Clin Pharmacol 1986; 26: 208–10

    PubMed  CAS  Google Scholar 

  56. 56.

    Scavone JM, Greenblatt DJ, Goddard JE, et al. The pharmacokinetics and pharmacodynamics of sublingual and oral alprazolam in the post-prandial state. Eur J Clin Pharmacol 1992; 42: 439–43

    PubMed  CAS  Google Scholar 

  57. 57.

    Schols-Hendriks MWG, Lohman JJHM, Janknegt R, et al. Absorption of clonazepam after intranasal and buccal administration. Br J Clin Pharmacol 1995; 39: 449–51

    PubMed  CAS  Article  Google Scholar 

  58. 58.

    Berthold CW, Dionne RA, Corey SE. Comparison of sublingually and orally administered triazolam for premedication before oral surgery. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997; 84(2): 119–24

    PubMed  CAS  Article  Google Scholar 

  59. 59.

    Gram-Hansen P, Schultz A. Plasma concentrations following oral and sublingual administration of lorazepam. Int J Clin Pharmacol Ther Toxicol 1988; 26(6): 323–4

    PubMed  CAS  Google Scholar 

  60. 60.

    Yager JY, Seshia SS. Sublingual lorazepam in childhood serial seizures. Am J Dis Child 1988 Sep; 142: 931–2

    PubMed  CAS  Google Scholar 

  61. 61.

    Hüttel MS, Bang U, Flachs H. Plasma concentrations of flunitrazepam (Rohypnol®) following oral and sublingual administration. Int J Clin Pharmacol 1986; 24(4): 221–3

    Google Scholar 

  62. 62.

    Streisand JB, Jaarsma RL, Gay MA, et al. Oral transmucosal etomidate in volunteers. Anesthesiology 1998; 88(1): 89–95

    PubMed  CAS  Article  Google Scholar 

  63. 63.

    Egan TD, Roland CL, White JL, et al. A proof of concept study of oral transmucosal etomidate (OTS™ etomidate) in volunteers [abstract]. American Society of Anesthesiology Annual Meeting; 2000 Oct 14–18; San Francisco (CA)

    Google Scholar 

  64. 64.

    Kern SE, Roland CL, White JL, et al. PK/PD analysis of etomidate given across the buccal mucosa [abstract]. American Society of Anesthesiology Annual Meeting; 2000 Oct 14–18; San Francisco (CA)

    Google Scholar 

  65. 65.

    Golding JF, Phil D, Gosden E, et al. Scopolamine blood levels following buccal versus ingested tablets. Aviat Space Environ Med 1991; 62: 521–6

    PubMed  CAS  Google Scholar 

  66. 66.

    Norfleet WT, Degioanni JJ, Calkins DS, et al. Treatment of motion sickness in parabolic flight with buccal scopolamine. Aviat Space Environ Med 1992; 63: 46–51

    PubMed  CAS  Google Scholar 

  67. 67.

    Hessell PG, Lloyd Jones JG, Muir NC, et al. A comparison of the availability of prochlorperazine following i.m. buccal and oral administration. Int J Pharm 1989; 52: 159–64

    CAS  Article  Google Scholar 

  68. 68.

    Ward AE. Studies of prochlorperazine as a buccal tablet (Buccastem) and an oral tablet (Stemetil) for the treatment of dizziness, nausea or vomiting in a general practice setting. Br J Clin Pract 1988; 42(6): 228–32

    PubMed  CAS  Google Scholar 

  69. 69.

    Singh S, Sharma DR, Chaudhary A. Evaluation of prochlorperazine buccal tablets (Bukatel) and metoclopramide oral tablets in the treatment of acute emesis. J Indian Med Assoc 1999 Aug; 97(8): 346–7

    PubMed  CAS  Google Scholar 

  70. 70.

    Williams PI, Smith M. An assessment of prochlorperazine buccal for the prevention of nausea and vomiting during intravenous patient-controlled analgesia with morphine following abdominal hysterectomy. Eur J Anaesth 1999; 16: 638–45

    CAS  Google Scholar 

  71. 71.

    Van Laar T, Neef C, Danhof M, et al. A new sublingual formulation of apomorphine in the treatment of patients with Parkinson’s disease. Mov Disord 1996; 11(6): 633–8

    PubMed  Article  Google Scholar 

  72. 72.

    Heaton JPW, Morales A, Adams MA, et al. Recovery of erectile function by the oral administration of apomorphine. Urology 1995 Feb; 45(2): 200–6

    PubMed  CAS  Article  Google Scholar 

  73. 73.

    Dula E, Keating W, Siami PF, et al. Efficacy and safety of fixed-dose and dose-optimization regimens of sublingual apomorphine versus placebo in men with erectile dysfunction. Urology 2000; 56: 130–5

    PubMed  CAS  Article  Google Scholar 

  74. 74.

    Durif F, Paire M, Deffond D, et al. Relation between clinical efficacy and pharmacokinetic parameters after sublingual apomorphine in Parkinson’s disease. Clin Neuropharmacol 1993; 16(2): 157–66

    PubMed  CAS  Article  Google Scholar 

  75. 75.

    Ondo W, Hunter C, Almaguer M, et al. A novel sublingual apomorphine treatment for patients with fluctuating Parkinson’s disease. Mov Disord 1999; 14(4): 664–8

    PubMed  CAS  Article  Google Scholar 

  76. 76.

    Zorgniotti AW. Experience with buccal phentolamine mesylate for impotence. Int J Impot Res 1994; 6: 37–41

    PubMed  CAS  Google Scholar 

  77. 77.

    Meikie AW, Mazer NA, Moellmen JF, et al. Enhanced transdermal delivery of testosterone across nonscrotal skin produces physiological concentrations of testosterone and its metabolites in hypogonadal men. J Clin Endocrinol Metab 1992; 74: 623–8

    Article  Google Scholar 

  78. 78.

    Seokjoong K, Snipes W, Hodgen GD, et al. Pharmacokinetics of a single dose of buccal testosterone. Contraception 1995; 52: 313–6

    Article  Google Scholar 

  79. 79.

    Salehian B, Wang C, Alexander G, et al. Pharmacokinetics, bioefficacy, and safety of sublingual testosterone cyclodextrin in hypogonadal men: comparison to testosterone enanthate -a Clinical Research Center study. J Clin Endocrinol Metab 1995; 80: 3567–75

    PubMed  CAS  Article  Google Scholar 

  80. 80.

    Dobs A, Hoover DR, Chen M, et al. Pharmacokinetic characteristics, efficacy, and safety of buccal testosterone in hypogonadal males: a pilot study. J Clin Endocrinol Metab 1998; 83(1): 33–9

    PubMed  CAS  Article  Google Scholar 

  81. 81.

    Wang C, Eyre DR, Clark R, et al. Sublingual testosterone replacement improves muscle mass and strength, decreases bone resorption, and increases bone formation markers in hypogonadal men: a Clinical Research Center study. J Clin Endocrinol Metab 1996; 81(10): 3654–62

    PubMed  CAS  Article  Google Scholar 

  82. 82.

    Wang C, Alexander G, Berman N, et al. Testosterone replacement therapy improves mood in hypogonadal men -a Clinical Research Center study. J Clin Endocrinol Metab 1996; 81(10): 3578–83

    PubMed  CAS  Article  Google Scholar 

  83. 83.

    Tuiten A, Van Honk J, Koppeschaar H, et al. Time course of effects of testosterone administration on sexual arousal in women. Arch Gen Psychiatr 2000 Feb; 57: 149–53

    PubMed  CAS  Article  Google Scholar 

  84. 84.

    Collins P, Rosano GMC, Sarrel PM, et al. 17β-estradiol attenuates acetylcholine-induced coronary arterial constriction in women but not men with coronary artery disease. Circulation 1995; 92: 24–30

    PubMed  CAS  Article  Google Scholar 

  85. 85.

    Volterrani M, Rosano G, Coats A, et al. Estrogen acutely increases peripheral blood flow in postmenopausal women. Am J Med 1995 Aug; 99: 119–22

    PubMed  CAS  Article  Google Scholar 

  86. 86.

    Gilligan DM, Quyyumi AA, Cannon III RO. Effects of physiological levels of estrogen on coronary vasomotor function in postmenopausal women. Circulation 1994; 89: 2545–51

    PubMed  CAS  Article  Google Scholar 

  87. 87.

    Pines A, Averbuch M, Fisman EZ, et al. The acute effects of sublingual 17β-estradiol on the cardiovascular system. Maturitas 1999; 33: 81–5

    PubMed  CAS  Article  Google Scholar 

  88. 88.

    Al-Khalili F, Landgren BM, Eksborg A, et al. Does sublingual 17β-oestradiol have any effects on exercise capacity and myocardial ischaemia in post-menopausal women with stable coronary artery disease? Eur Heart J 1998 Jul; 19: 1019–26

    PubMed  CAS  Article  Google Scholar 

  89. 89.

    Hoon TJ, Dawood Y, Khan-Dawood FS, et al. Bioequivalence of a 17β-estradiol hydroxypropyl-β-cyclodextrin complex in postmenopausal women. J Clin Pharmacol 1993; 33: 1116–21

    PubMed  CAS  Google Scholar 

  90. 90.

    Price TM, Blauer KL, Hansen M, et al. Single-dose pharmacokinetics of sublingual versus oral administration of micronized 17β-estradiol. Obstet Gynecol 1997 Mar; 89(3): 340–5

    PubMed  CAS  Article  Google Scholar 

  91. 91.

    Svensson CK. Clinical pharmacokinetics of nicotine. Clin Pharmacokinet 1987; 12: 30–40

    PubMed  CAS  Article  Google Scholar 

  92. 92.

    Zobrist RH, Marriott JG, Nordbrock EN, et al. Nicotine administration with a new oral transmucosal delivery system: a dose response study. Second Annual Scientific Conference of the Society for Research on Nicotine and Tobacco; 1996 Mar 15–17; Washington, DC

    Google Scholar 

  93. 93.

    Zobrist RH, Marriott JG, Gilbert R, et al. Preliminary eight week safety and efficacy of oral transmucosal nicotine (OT-nicotine) compared to patch and gum for smoking cessation [abstract no. B50]. Third Annual Scientific Conference of the Society for Research on Nicotine and Tobacco; 1997 Jun; Nashville (TN)

    Google Scholar 

  94. 94.

    Gutniak MK, Orskov C, Holst JJ, et al. Antidiabetogenic effect of glucagon-like peptide-1 (7-36) amide in normal subjects and patients with diabetes mellitus. New Engl J Med 1992; 326(20): 1316–22

    PubMed  CAS  Article  Google Scholar 

  95. 95.

    Gutniak MK, Larsson H, Heiber SJ, et al. Potential therapeutic levels of glucagon-like peptide I achieved in humans by a buccal tablet. Diabetes Care 1996; 19(8): 843–8

    PubMed  CAS  Article  Google Scholar 

  96. 96.

    Gutniak MK, Larsson H, Sanders SW, et al. GLP-1 tablet in type 2 diabetes in fasting and postprandial conditions. Diabetes Care 1997; 20(12): 1874–9

    PubMed  CAS  Article  Google Scholar 

  97. 97.

    Al-Waili NS. Sublingual human insulin for hyperglycaemia in type I diabetes. J Pak Med Assoc 1999; 49(7): 167–9

    PubMed  CAS  Google Scholar 

  98. 98.

    Edwards CRW, Kitau MJ, Chard T, et al. Vasopressin analogue DDAVP in diabetes insipidus: clinical and laboratory studies. BMJ 1973; 3: 375–8

    PubMed  CAS  Article  Google Scholar 

  99. 99.

    Grossman A, Fabbri A, Goldberg PL, et al. Two new modes of desmopressin (DDAVP) administration. BMJ 1980; 280(6225): 1215

    PubMed  CAS  Article  Google Scholar 

  100. 100.

    Laczi F, Mezei G, Julesz J, et al. Effects of vasopressin analogues (DDAVP, DVDAVP) in the form of sublingual tablets in central diabetes insipidus. Int J Clin Pharmacol Ther Toxicol 1980; 18(12): 63–8

    Google Scholar 

  101. 101.

    Fjellestad-Paulsen A, Hoglund P, Lundin S, et al. Pharmacokinetics of 1-deamino-8-D-arginine vasopressin after various routes of administration in healthy volunteers. Clin Endocrinol 1993; 38: 177–82

    CAS  Article  Google Scholar 

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Acknowledgements

The authors thank Lynne F. Pauley, M.S., for her research and editorial assistance. No sources of funding were used to assist in the preparation of this manuscript. There are no potential conflicts of interest directly relevant to the contents of this manuscript.

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Zhang, H., Zhang, J. & Streisand, J.B. Oral Mucosal Drug Delivery. Clin Pharmacokinet 41, 661–680 (2002). https://doi.org/10.2165/00003088-200241090-00003

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Keywords

  • Oral Mucosa
  • Etomidate
  • Motion Sickness
  • Propafenone
  • Sublingual Administration