Summary
19 healthy volunteers wore a nitroglycerin patch releasing 10 mg per 24 h for 2 h. Subsequently, the skin area surrounding the patch was exposed to 15 min of local heating with an infrared bulb (Group A, n =10), or local cooling with an ice-pack (Group B, n = 9). The patch was protected by an insulating shield (Styrofoam).
After 10 min of heating, the median (Walsh) plasma nitroglycerin level increased from 3.1 to 7.6 nmol·1−1. Body temperature remained constant. After 15 min of cooling the median plasma level had dropped from 2.1 to 1.4 nmol·1−1.
The results demonstrate that changes in skin temperature may cause extensive short-term changes in the bioavailability of nitroglycerin. Presumably, a subcutaneous or cutaneous reservoir builds up during transdermal treatment, and changes in regional cutaneous blood flow affect the rate of drainage from the reservoir into the systemic circulation.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Nimmo WS (1990) The promise of transdermal drug delivery. Br J Anesth 64: 7–10
Chien YW (1984) Pharmaceutical considerations of transdermal nitroglycerin delivery: The various approaches. Am Heart J 108: 207–216
Barkve TF, Langseth-Manrique K, Bredesen JE, Gjesdal K (1986) Increased uptake of transdermal glyceryl trinitrate during physical exercise and during high ambient temperature. Am Heart J 112:537–541
Weber S, de Lauture D, Rey E, Darragon T, Severins JP, Ditisheim A, Olive G, Degeorges M (1987) The effects of moderate sustained exercise on the pharmacokinetics of nitroglycerin. Br J Clin Pharmacol 23: 103–105
Lefebvre RA, Bogaert MG, Teirlynck O, Sioufi A, Dubois JP (1990) Influence of exercise on nitroglycerin plasma concentrations after transdermal application. Br J Clin Pharmacol 30: 292–296
Gjesdal K, Klemsdal TO, Rkrykke E, Bredesen E, (1991) Transdermal nitrate therapy: bioavailability during exercise increases transiently after the daily change of patch. Br J Clin Pharmacol 31: 560–562
Müller P, Imhof PR, Burkart F, Chu LC, Gerardin A (1982) Human pharmacological studies on a new transdermal system containing nitroglycerin. Eur J Clin Pharmacol 22: 473–480
Karim A (1983) Transdermal absorption of nitroglycerin from microseal drug delivery (MDD) system. Angiology 34:11–22
Lindberg LG, Tamura T, Öberg PA (1991) Photoplethysmography. Part 1. Comparison with laser Doppler flowmetry. Med Biol Eng Comput 29: 40–47
Langseth-Manrique K, Bredesen JE, Greibrokk T (1985) Rapid isothermal gas-liquid chromatographic determination of nitroglycerin in plasma with use of an electron capture detector II. J Chromatogr 349: 421–424
Yum SI (1989) Transdermal therapeutic systems and rate controlled drug delivery. Med Prog Technol 15: 47–52
Wolff HM, Bonn R (1989) Principles of transdermal nitroglycerin administration. Eur Heart J 10 [Suppl A]: 26–29
Shaw JE (1984) Pharmacokinetics of nitroglycerin and clonidine delivered by the transdermal route. Am Heart J 108: 217–223
Mcniff EF, Yacobi A, Young-Chang FM, Golden LH, Goldfarb A, Fung HL (1981) Nitroglycerin pharmacokinetics after intravenous infusion in normal subjects. J Pharm Sci 70: 1054–1058
Schneider W, Kaltenbach M (1986) Dosiswirkungsbeziehungen bei der Therapie der Angina pectoris mit Nitraten. Z Kardiol 75: 61–67
Metelitsa VI, Martsevich SY, Piotrovskii VK, Ryabokon OS, Blagodatskikh SV (1987) New transdermal and transmucosal nitro-glycerin delivery systems in patients with ischemic heart disease. Eur J Clin Pharmacol 32: 5–10
Imhof PR, Ott B, Frankhauser P, Chu LC, Hodler J (1980) Difference in nitroglycerin dose-response in the venous and arterial beds. Eur J Clin Pharmacol 18: 455–460
Parker JO, Fung HL (1984) Transdermal nitroglycerin in angina pectoris. Am J Cardiol 54: 471–476
Bogaert MG (1987) Clinical pharmacokinetics of glyceryl trinitrate following the use of systemic and topical preparations. Clin Pharmacokinet 12: 1–11
Gumbleton M, Benet LZ (1990) Pharmacological activity of the dinitrate metabolites of nitroglycerin following their oral administration to healthy volunteers. Br J Clin Pharmacol 31: 211–213
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Klemsdal, T.O., Gjesdal, K. & Bredesen, J.E. Heating and cooling of the nitroglycerin patch application area modify the plasma level of nitroglycerin. Eur J Clin Pharmacol 43, 625–628 (1992). https://doi.org/10.1007/BF02284961
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02284961