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Buprederm™, a New Transdermal Delivery System of Buprenorphine: Pharmacokinetic, Efficacy and Skin Irritancy Studies

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Abstract

Purpose

The pharmacokinetics, analgesic efficacy, and irritancy potential of Buprederm™, a new transdermal delivery system of buprenorphine, was evaluated.

Methods

Single and multiple dose pharmacokinetic studies were conducted in mice and rabbits. The analgesic efficacy and skin irritation potential were determined by tail flick and writhing tests in mice and by the Draize dermal scoring system in rabbits.

Results

Fast absorption of buprenorphine into the bloodstream was observed in mice and rabbits after Buprederm™ application. The peak buprenorphine level in plasma was achieved between 1 and 24 h, and the effective therapeutic drug concentration was maintained for 72 h. No significant accumulation of buprenorphine was seen after multiple consecutive applications of patches to rabbits with a 4-day dosing interval. Buprederm™ induced prolongation of tail-flick latency in a dose- and time-dependent manner. Maximum analgesic effect was attained between 3 and 6 h and was maintained for 24 h after patch application. No skin irritation was demonstrated in rabbits after repeated Buprederm™ application.

Conclusions

Buprederm™ was shown to be efficacious by achieving the effective buprenorphine concentration in the blood and brain sufficient to maintain an analgesic effect for 72 h, and was also shown to be safe following multiple applications.

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Abbreviations

BBB:

Blood–brain barrier

BTDS:

Buprenorphine transdermal system

HPLC:

High performance liquid chromatography

IS:

Internal standard

LC/MS/MS:

Liquid chromatography-tandem mass spectrometry

LOQ:

Limit of quantification

ME:

Maximum effect

MeOH:

Methanol

MRM:

Multiple reaction monitoring

P-gp :

P-glycoprotein

PK/PD:

Pharmacokinetic/pharmacodynamic

S.D.:

Standard deviation

S.E.M.:

Standard error of means

TDS:

Transdermal delivery system

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Acknowledgements

We would like to thank Dr. Chad Brown for his help in preparation of this manuscript and Mr. Jae Hee Jang for his skillful technical support. The authors acknowledge Yun Jeong Kim and Seung Jin Baek of Biotoxtech, Korea, for conducting the skin irritation and analgesic experiments.

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  1. Samyang Pharmaceutical R&D Center, 63-2 Hwaam-dong, Yuseong-gu, Daejeon, 305-717, Republic of Korea

    In Park, Dongwon Kim, Jindeog Song, Chang Hoon In, Seung-Wei Jeong, Sang Hun Lee, Bumchan Min, Dongho Lee & Sun-Ok Kim

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  1. In Park
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Park, I., Kim, D., Song, J. et al. Buprederm™, a New Transdermal Delivery System of Buprenorphine: Pharmacokinetic, Efficacy and Skin Irritancy Studies. Pharm Res 25, 1052–1062 (2008). https://doi.org/10.1007/s11095-007-9470-6

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