The pharmacokinetics of transdermal fentanyl delivered with and without controlled heat

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.…”

Plasma Fentanyl Concentrations Achieved after Transdermal Fentanyl Patch Application in Prehensile-Tailed Skinks, Corucia zebrata

“…N ot only would this measurement be expected for a heterothermic species to consider its impact on drug metabolic pathways but also it has been documented that increased external heat at T D F can increase absorption from the patches into the patient (Thompson and Rowbotham, 2002;Ashburn et al, 2003;Hofmeister and Egger, 2004). Because the curves analyzed with good modeling statistical parameters for three skinks, consistent parameters were observed for each individual, and only one skink achieved elevated concentra tions compared with the others, I considered that basking point temperatures did not markedly impact TD F absorp tion for this study.…”

“…However, the impact of heat on fentanyl in patch formulation must be considered in clinical situa tions, in which animals may bask for longer duration because o f a behavioral fever, or in surgical situations in which external sources o f warmth, such as recirculating water blankets, are used. In these situations, effects of exces sive fentanyl absorption or reduced lag time to absorption could be encountered (Ashburn et al, 2003).…”

“…Although the scale (stratum germinivatum) layer is the thickest layer, it is also lipid-soluble; so, systemic fentanyl absorption should occur via the transdermal route (Rossi, 1996;Glerum et al, 2001;Gellasch et al, 2002), as occurs with mammals. Time to reach systemic fentanyl concentrations associated with clinical analgesia will vary by individual, by species, ambient heat, and thickness and health o f the skin (Riviere and Papich, 2001;Ashburn et al, 2003;Mills et al, 2004). T D F absorption does have a mini mal 6-8-h lag from patch application in domestic mammals and hum ans (Lee et al, 2000).…”

Transdermal fentanyl: Pharmacology and toxicology

“…Skin temperature elevation enhances the absorption of transdermally-applied fentanyl, perhaps either as a result of cutaneous vasodilation or of enhanced solubility of fentanyl [51][52][53]. An increase in skin temperature from 32°C to 40°C leads to a gradual 10-to 15-fold increase in cutaneous blood flow [54].…”