Assessing the Impact of Heat on the Systemic Delivery of Fentanyl Through the Transdermal Fentanyl Delivery System

Shomaker, JD T. Samuel; Zhang, Jie; Ashburn, Mph Michael A.

doi:10.1046/j.1526-4637.2000.00030.x

Cited by 64 publications

(44 citation statements)

References 18 publications

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“…12 [16,17]. Therefore, these results confirm that the 12-h conversion method provides an effective treatment for cancer pain, but adverse events occurred in approximately 20% of patients.…”

Section: Discussionsupporting

confidence: 67%

Six- versus 12-h conversion method from intravenous to transdermal fentanyl in chronic cancer pain: a randomized study

Nomura

Kamata

Kojima

et al. 2010

Support Care Cancer

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“…12 [16,17]. Therefore, these results confirm that the 12-h conversion method provides an effective treatment for cancer pain, but adverse events occurred in approximately 20% of patients.…”

Section: Discussionsupporting

confidence: 67%

Six- versus 12-h conversion method from intravenous to transdermal fentanyl in chronic cancer pain: a randomized study

Nomura

Kamata

Kojima

et al. 2010

Support Care Cancer

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“…Previous studies have emphasized either long exposures at moderate temperatures or very short exposures at high temperatures. As an example of extended heating at moderate temperature, exposure to 40 • C for 4 h has been shown to increase human skin permeability to a hydrophobic drug (fentanyl) by 4-fold via a mechanism believed to involve stratum corneum lipid fluidization (Shomaker et al, 2000). Exposure to 80 • C for 15 s showed a 12-fold increase in porcine skin permeability to another hydrophobic model drug, butanol (Flynn et al, 1982).…”

Section: Introductionmentioning

confidence: 99%

The effect of heat on skin permeability

Park¹,

Lee

Kim

et al. 2008

International Journal of Pharmaceutics

111

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a b s t r a c tAlthough the effects of long exposure ( 1 s) to moderate temperatures (≤100 • C) have been well characterized, recent studies suggest that shorter exposure (<1 s) to higher temperatures (>100 • C) can dramatically increase skin permeability. Previous studies suggest that by keeping exposures short, thermal damage can be localized to the stratum corneum without damaging deeper tissue. Initial clinical trials have progressed to Phase II (see http://clinicaltrials.gov), which indicates the procedure can be safe. Because the effect of heating under these conditions has received little systematic or mechanistic study, we heated full-thickness skin, epidermis and stratum corneum samples from human and porcine cadavers to temperatures ranging from 100 to 315 • C for times ranging from 100 ms to 5 s. Tissue samples were analyzed using skin permeability measurements, differential scanning calorimetry, thermomechanical analysis, thermal gravimetric analysis, brightfield and confocal microscopy, and histology. Skin permeability was shown to be a very strong function of temperature and a less strong function of the duration of heating. At optimal conditions used in this study, transdermal delivery of calcein was increased up to 760-fold by rapidly heating the skin at high temperature. More specifically, skin permeability was increased (I) by a few fold after heating to approximately 100-150 • C, (II) by one to two orders of magnitude after heating to approximately 150-250 • C and (III) by three orders of magnitude after heating above 300 • C. These permeability changes were attributed to (I) disordering of stratum corneum lipid structure, (II) disruption of stratum corneum keratin network structure and (III) decomposition and vaporization of keratin to create micron-scale holes in the stratum corneum, respectively. We conclude that heating the skin with short, high temperature pulses can increase skin permeability by orders of magnitude due to structural disruption and removal of stratum corneum.

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“…10 Other studies identified that heat and/or elevated skin temperature increased the absorption of transdermal fentanyl, probably secondary to vasodilation of cutaneous vasculature. [11][12][13] In addition, many case reports have described a potential or actual fentanyl overdose following exposure to external heat sources including hot tubs, heating blankets, saunas and sunbathing. [13][14][15] As transdermal fentanyl administration avoids first-pass hepatic metabolism, it achieves an excellent bioavailability ($92%), most of which is protein bound (84%).…”

Section: Pharmacological Properties Of Transdermal Fentanylmentioning

confidence: 99%

A case of overdose via tattoo

Borg

Ashton

2015

Journal of the Intensive Care Society

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Transdermal fentanyl patches are used frequently for the management of both acute and chronic pain. Adverse events with their use, in particular overdose, are not uncommon. We describe a case of fentanyl overdose from transdermal patch placed over a five-day old tattoo. The report will review the pharmacology of transdermal fentanyl and the physiology of tattooing, as well as the potential link between the two, which may have lead to the overdose. Keywords Fentanyl, transdermal patch, drug overdose, tattooingFentanyl is a potent opioid used to control acute and chronic pain. While the transdermal delivery of fentanyl is deemed safe and effective in alleviating moderate to severe chronic pain, 1 there have been several reported cases of its intentional or unintentional misuse and abuse leading to significant clinical consequences, including death.2 Both the US Food and Drug Administration and the UK Medicines and Healthcare Products Regulatory Agency (MHRA) 3,4 have previously issued drug safety warnings on the use of fentanyl patches. These were in response to investigations of overdoses of fentanyl due to dosing errors, accidental exposure and exposure of the patch to a heat source. We describe an unintentional, lifethreatening overdose of fentanyl from a transdermal patch placed over a five-day old tattoo, which to our knowledge has not been previously reported. Case reportA 56-year-old male was brought by ambulance to the emergency department having been found at home by his friend to be drowsy and cyanosed. His past medical history included type 2 diabetes mellitus, hypertension, bipolar depressive disorder and chronic back pain. Regular medications were aspirin 75 mg mane, atorvastatin 40 mg mane, citalopram 20 mg mane, fentanyl transdermal patch 100 mcg 72 hourly, human insulin 16 units mane and 14 units nocte, metformin 1G bd and sodium valproate 500 mg mane and 1 g nocte. He was also prescribed as required tramadol 100 mg and naproxen 250 mg.On examination there was a patent airway, respiratory rate of 12 breaths per minute, peripheral oxygen saturations of 92% breathing room air. Blood pressure was 110/75 mmHg, heart rate of 83 beats/min and temperature 36.7 C. His Glasgow Coma Score was fluctuating between E2 V3 M5 and E3 V5 M6 at best. Pupils were 2 mm bilaterally and reactive to light and capillary blood glucose 11.4 mmol/l. He was also acidotic with a pH of 7.24 and PaCO 2 of 9.03 (BE -0.2 mmol/l, HCO 3 28.6 mmol/l).A collateral history from the patient's friend was obtained: the patient had been completely well the evening before the incident; he had become intermittently confused on the afternoon when she found him and had called for an ambulance as he became increasingly drowsy and blue around the lips. She denied witnessing any seizure-like activity, the use of recreational drugs or deliberate overdose. The patient had a similar presentation to the Emergency Department six months previously, with normal findings on an EEG, CT brain and lumbar puncture. At the time he was found to have mi...

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Assessing the Impact of Heat on the Systemic Delivery of Fentanyl Through the Transdermal Fentanyl Delivery System

Abstract: Local heat can speed the onset of steady state fentanyl concentration in the Fentanyl Transdermal Drug Delivery System thus limiting the delay in onset of analgesia and allowing earlier identification and treatment of side effects.

Cited by 64 publications

References 18 publications

Six- versus 12-h conversion method from intravenous to transdermal fentanyl in chronic cancer pain: a randomized study

Six- versus 12-h conversion method from intravenous to transdermal fentanyl in chronic cancer pain: a randomized study

The effect of heat on skin permeability

A case of overdose via tattoo

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