Original Article

Journal of Investigative Dermatology (1995) 104, 839–843; doi:10.1111/1523-1747.ep12607019

Microdialysis in Cutaneous Pharmacology: Kinetic Analysis of Transdermally Delivered Nicotine

Lutz Hegemann, Christa Forstinger, Bernhard Partsch, Irmgard Lagler, Sabine Krotz and Klaus Wolff

Dermatopharmacology Unit, Department of Dermatology, Division of General Dermatology, University of Vienna, Vienna, Austria

Received 19 October 1994; Revised 20 January 1995; Accepted 27 January 1995.

Top

Abstract

Direct measurements of cutaneous drug levels and kinetics have long been hampered by lack of appropriate methods, Recently, studies have indicated that microdialysis, a method of continuous in vivo sampling of extracellular fluid, may also be performed in human skin. The present study was designed to evaluate this technique for kinetic analyses of cutaneous drug levels. Using a transdermal nicotine delivery system with 35 mg of nicotine as a model, nicotine levels were determined in the dialysate of human skin by means of high performance liquid chromatography. In vitro studies demonstrated that nicotine levels in the dialysate strictly correlated with nicotine concentrations in the dialyzed medium, In nine healthy male volunteers receiving nicotine by transdermal delivery, nicotine was detectable within 90–180 min, and peak levels of approximately 1000 ng/ml were detected within 240–360 min of patch application. Correlation analyses of the individual data from our subjects revealed that nicotine kinetics were independent of skin barrier function, as assessed by transepidermal water loss, but indicated that the detectable maximum nicotine levels may depend on the location of the probe. In summary, the present study demonstrates that microdialysis may be a novel, powerful tool to study cutaneous pharmocology in vivo.

Keywords:

human skin, ultrasonography, transepidermal water loss, drug levels

Top

References

  1. Kiistala, U, Mustakallio, KK: Dermo-epidermal separation with suction. J Invest Dermatol 48: 466–477, 1967 | PubMed | ISI | ChemPort |
  2. Ungerstedt, U: Microdialysis–principles and applications for studies in animals and man. J Intern Med 230: 365–373, 1991 | PubMed | ChemPort |
  3. Ståhle, L, Arner, P, Ungerstedt, U: Drug distribution studies with microdialysis. III: Extracellular concentration of caffeine in adipose tissue in man. Life Sci 49: 1853–1858, 1991
  4. Ståhle, L, Guzenda, E, Ljungdahl-Ståhle, E: Pharmacokinetics and extracellular distribution to blood, brain, and muscle of alovudine (3'-fluorothymidine) and zidovudine in the rat studied by microdialysis. J Acquir Immune Defic Syndr 6: 435–439, 1993
  5. Petersen, LJ, Kristensen, JK, Bülow, J: Microdialysis of the interstitial water space in human skin in vivo: quantitative measurements of cutaneous glucose concentrations. J Invest Dermatol 99: 357–360, 1992
  6. Petersen, LJ, Stahl Skov, P, Bindslev-Jensen, C, Søndergaard, J: Histamine release in immediate-type hypersensitivity reactions in intact human skin measured by microdialysis. Allergy 47: 635–637, 1992
  7. Anderson, C, Andersson, T, Andersson, RGG: In vivo microdialysis estimation of histamine in human skin. Skin Pharmacol 5: 177–183, 1992
  8. Anderson, C, Andersson, T, Molander, M: Ethanol absorption across human skin measured by in vivo microdialysis technique. Acta Derm Venereol (Stockh) 71: 389–393, 1991
  9. Tupker, RA, Pinnagoda, J, Coenraads, PJ, Nater, JP: Transepidermal water loss measurement by means of an evaporimeter. In: Frosch PJ, Kligman AM (eds.), Noninvasive Methods for the Quantification of Skin Functions Springer Verlag, Berlin, pp 56–70, 1993
  10. Serup, J: Ten years' experience with high-frequency ultrasound examination of the skin: development and refinement of technique and equipment. In: Alomeyer P, el-Gammal S, Hoffmann K (eds.). Ultrasound in Dermatology Springer Verlag, Berlin, pp 41–55, 1992
  11. el-Gammal, S, Auer, T, Hoffmann, K, Matthes, U, Hammentgen, R, Altmeyer, P, Ermert, H: High-frequency ultrasound: a noninvasive method for use in dermatology. In: Frosch PJ, Kligman AM (eds.). Noninvasive Methods for the Quantification of Skin Functions Springer Verlag, Berlin, pp 104–129, 1993
  12. Horstmann, M: Simple high-performance liquid chromatographic method for rapid determination of nicotine and cotinine in urine. J Chromatogr 344: 391–396, 1985
  13. Hamberger, A, Jacobson, I, Nyström, B, Sandberg, M: Microdialysis sampling of the neuronal environment in basic and clinical research. J Intern Med 230: 375–380, 1991
  14. Dubois, J, Sioufi, A, Müller, P, Mauli, D, Imhof, PR: Pharmacokinetics and bioavailability of nicotine in healthy volunteers following single and repeated administration of different doses of transdermal nicotine systems. Methods Find Exp Clin Pharmacol 11: 187–195, 1989
  15. Müller, P, Imhof, PR, Mauli, D, Milovanovic, D: Human pharmacological investigations of a transdermal nicotine system. Methods Find Exp Clin Pharmacol 11: 197–204, 1989
  16. Anderson, C, Andersson, T, Wårdell, K: Changes in skin circulation after insertion of a microdialysis probe visualized by laser Doppler perfusion imaging. J Invest Dermatol 102: 807–811, 1994 | Article | PubMed | ISI | ChemPort |
  17. Elias, PM: Structure and function of the stratum corneum permeability barrier. Drug Dev Res 13: 97–105, 1988
  18. Smith, EW, Smith, KA, Maibach, HI, Andersson, PO, Cleary, G, Wilson, D: The local side effects of transdermally absorbed nicotine. Skin Pharmacol 5: 69–76, 1992 | PubMed | ISI | ChemPort |
  19. Ståhle, L: Pharmacokinetic estimations from microdialysis data. Eur J Clin Pharmacol 43: 289–294, 1992 | PubMed | ChemPort |

Extra navigation

.
ADVERTISEMENT