Evaluation of a transdermal buprenorphine formulation in opioid detoxification.
OBJECTIVE
Buprenorphine is marketed in a sublingual formulation for treatment of opioid dependence. A transdermal formulation has been developed that may provide extended relief from opioid withdrawal, reduce required clinic visits and improve adherence, while having less potential for diversion and abuse. This study evaluated the safety and biodelivery (blood levels) of this transdermal buprenorphine formulation (i.e. buprenorphine patch), and its apparent efficacy in suppressing the opioid withdrawal syndrome.


METHODS
Open-label, first-in-humans trial.


METHODS
A residential research facility.


METHODS
Nine physically dependent opioid-users completed the 10-day opioid detoxification study.


METHODS
Each volunteer received a single patch application that remained in place for 3 days. The formulation has shown an average delivery of 1.9 mg/day of buprenorphine over 3 days in pre-clinical evaluation.


METHODS
Physiological, behavioral, subjective and observer ratings of opioid withdrawal and opioid agonist effects were collected.


RESULTS
Overall, the patch appeared safe and well tolerated. There were no serious adverse events, and no opioid intoxication following patch application. Oxygen saturation, heart rate, blood pressure, skin temperature and pupil diameter remained well within normal ranges. Buprenorphine blood levels peaked 48 hours after patch application at a concentration of 0.60 ng/ml. Volunteers' self-reports of the presence and severity of withdrawal symptoms were reduced by approximately 50% on the 3 days of patch application. Withdrawal symptoms increased marginally upon patch removal. Administration of opioid rescue medication was eliminated within 6 hours of patch application, and increased slightly upon patch removal.


CONCLUSIONS
The significant biodelivery of buprenorphine and the suppression of the opioid withdrawal syndrome during patch application and its reappearance after patch removal indicate clinically useful pharmacodynamic activity. Transdermal buprenorphine may be a useful opioid detoxification treatment that reduces compliance concerns, and delivers buprenorphine in a formulation less likely to be diverted to illicit use.
Lanier
Ryan K
RK
Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA. rlanier1@jhmi.edu
Umbricht
Annie
A
Harrison
Joseph A
JA
Nuwayser
Elie S
ES
Bigelow
George E
GE
D000279:Administration, Cutaneous; D000328:Adult; D002047:Buprenorphine / Q000378:metabolism / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006556:Heroin Dependence / Q000523:psychology / Q000534:rehabilitation*; D006801:Humans; D008658:Inactivation, Metabolic; D008297:Male; D008875:Middle Aged; D009292:Narcotic Antagonists / Q000378:metabolism / Q000627:therapeutic use*; D013375:Substance Withdrawal Syndrome
D009292:Narcotic Antagonists; D002047:Buprenorphine