Heating and cooling of the nitroglycerin patch application area modify the plasma level of nitroglycerin

Abstract

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.l-1. Body temperature remained constant. After 15 min of cooling the median plasma level had dropped from 2.1 to 1.4 nmol.l-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.

Dermal and Transdermal Drug Delivery Systems: Current and Future Prospects

“…Under in vivo conditions, the increase in blood supply to the surface of the skin as a result of increased temperature also plays an important role in enhancing the transdermal delivery of a topically applied compound (Klemsdal, Gjesdal, and Bredesen 1992;Hull 2002). The in vivo delivery of nitroglycerin (Klemsdal et al 1992), testosterone, lidocaine, tetracaine (Shomaker, Zhang, and Ashburn 2001) and fentanyl (Ashburn et al 2003) from transdermal patches with attached heating devices was shown to increase as a result of the elevated temperature at the site of delivery. However, the effect of temperature on the delivery of penetrants over 500 Da has not been reported.…”

Transdermal Drug Delivery Systems: Skin Perturbation Devices

“…The increased permeation following heat treatment has been attributed to an increase in drug diffusivity in the vehicle and an increase in drug diffusivity in the skin due to increased lipid fluidity (57). Vasodilation of the subcutaneous blood vessels as a homeostatic response to a rise in skin temperature also plays an important role in enhancing the transdermal delivery of topically applied compounds (58,59). The in vivo delivery of nitroglycerin (58), testosterone, lidocaine, tetracaine (60) and fentanyl (61) from transdermal patches with attached heating devices was shown to increase as a result of the elevated temperature at the site of delivery.…”

Impacts of climate and climate change on medications and human health

“…11 Heat-induced local vasodilatation and acceleration of skin blood flow appear to be the main mechanisms leading to this change in absorption. 12 Vanakoski and Seppälä 11 also state that, "changes in the physicochemical properties of transdermal patches, sweating and increased humidity of the skin may contribute to the release and diffusion of transdermally administered drugs".…”