The isolated normothermic hemoperfused porcine forelimb as a test system for transdermal absorption studies

被引：21
作者：
Susanne M. Wagner
Ana C. Nogueira
Martin Paul
Dagmar Heydeck
Stephan Klug
Bruno Christ
机构：
[1] Vitro-Tec Entwicklungs-GmbH, 12247 Berlin
[2] Inst. for Clin. Pharmacol./Toxicol., Department of Toxicology, Free University, Berlin
来源：
Journal of Artificial Organs | 2003年 / 6卷 / 3期
关键词：
Extracorporeal circuit; Perfusion; Pig; Transdermal absorption;
D O I：
10.1007/s10047-003-0229-5
中图分类号：
学科分类号：
摘要：
For transdermal absorption studies, a porcine skin model that maintains the characteristics of the skin as close to physiological conditions as possible should be established because of the close similarity of porcine and human skin. Perfusion flow, glucose concentration, and oxygen supply were varied and organ resistance and lactate concentration were measured as parameters for organ performance. Transdermal absorption studies were performed using nitroglycerin or estradiol as test solutes. By the use of a standardized perfusion apparatus, limbs were perfused with a normothermic blood/electrolyte mix over a 6-h period. Organ resistance and lactate concentration were lower in limbs perfused with high flow as compared to perfusion with low flow. However, high perfusion flow caused an initial increase of hemolysis in the venous perfusate resulting in a higher concentration of free hemoglobin compared to low perfusion flow conditions. Glucose level in the perfusate was maintained within the porcine physiological range. By applying optimized conditions, the transdermal absorption of nitroglycerin or estradiol released from transdermal therapeutic systems was investigated. A time-dependent accumulation of the substances in the perfusion medium was observed, indicating the continuous uptake via the skin. After 6 h (nitroglycerin) or 5 h (estradiol) of perfusion, test substances accumulated to concentrations comparable to those described in hummans. In conclusion the perfused porcine limb may serve as a reliable test system for transdermal absorption studies. The model is suited to the replacement of animal testing and has a higher predictive potential because of the similarities of porcine and human skin.
引用
收藏
页码：183 / 191
页数：8
相关论文
共 38 条
  • [1] Kietzmann M., Loscher W., Die verwendung von schlachttierorganen zur prüfung von arzneimitteln: Eignung des rindereuters zur untersuchung von hautwirksamen stoffen, Dtsch Tierärztl Wschrift, 100, pp. 54-57, (1993)
  • [2] Grosse-Siestrup C., Fehrenberg C., Von Baeyer H., Groneberg D.A., Multiple-organ harvesting for models of isolated hemoperfused organs of slaughtered pigs, Altex, 19, pp. 9-13, (2002)
  • [3] Von Baeyer H., Stahl K., Hausler M., Meissler M., Unger V., Frank J., Grosse-Siestrup C., Kaczmarczyk G., Affeld K., Flaig H.-J., Steinbach B., Eine neue methode zur ex-vivo-vollblut-perfusion isolierter warmblüterorgane, dargestellt an der niere von schweinen, Biomedizinische Technik, 42, pp. 61-67, (1997)
  • [4] Pittermann W., Kietzmann M., Jackwerth B., Das isolierte perfundierte rindereuter (bovine udder skin-BUS modell): Ein integriertes in vitro modell zur untersuchung von hautpenetration und-irritation, Altex, 12, pp. 196-200, (1995)
  • [5] Bartek M.J., LaBudde J.A., Maibach H.I., Skin permeability in vivo: Comparison in rat, rabbit, pig and man, J Invest Dermatol, 58, pp. 114-123, (1972)
  • [6] Chang S.K., Williams P.L., Dauterman W.C., Riviere J.E., Percutaneous absorption, dermatopharmacokinetics and related bio-transformation studies of carbaryl, lindane, malathion, and parathion in isolated perfused porcine skin, Toxicology, 91, pp. 269-280, (1994)
  • [7] Godynicki S., Fath el-Bab M.R., Schwarz R., Distribution of blood vessels in the skin of pigs at birth, Anat Histol Embryol, 14, pp. 304-315, (1985)
  • [8] Meyer W., Bemerkungen zur eignung der schweinehaut als biologisches modell für die haut des menschen, Hautarzt, 47, pp. 178-182, (1996)
  • [9] Meyer W., Die Haut des Schweines, Band 9 Archiv für Tierärztliche Fortbildung, pp. 172-175, (1986)
  • [10] De Roux A., Dermale permeationsuntersuchungen an isolierten normotherm hämoperfundierten knochen-haut-muskelpräparaten am beispiel von lidocain aus xylocain gel 2%, Eine Ersatzmethode zum Tierversuch, (1999)
1234