title: Once-weekly transdermal buprenorphine application results in sustained and consistent steady-state plasma levels.
abstract: BACKGROUND
  Transdermal formulations of buprenorphine offer controlled delivery of buprenorphine for sustained analgesic efficacy with reduced adverse events (AEs) compared with the other modes of administration. A buprenorphine transdermal system (BTDS) delivering 5, 10, or 20 mcg/hour for seven days is now marketed in the U.S. as Butrans(®) (Lohmann Therapie-System AG, Andernach Germany), a Schedule III single-entity opioid analgesic indicated for the management of moderate and chronic pain in patients requiring continuous around-the-clock analgesia for an extended period.
  
  
  OBJECTIVE
  This was a randomized open-label study in healthy subjects to characterize the steady-state buprenorphine pharmacokinetics after the delivery of three consecutive seven-day BTDS applications.
  
  
  METHODS
  Thirty-seven subjects were randomized to receive three consecutive BTDS 10 mcg/hour (BTDS 10) patches applied to the deltoid or upper back for seven days each. Blood samples for buprenorphine concentration measurements were taken. Safety was assessed using recorded AEs, clinical laboratory test results, vital signs, pulse oximetry, physical examinations, and electrocardiograms. Patch adhesion assessments were taken.
  
  
  RESULTS
  Analysis of Cmin demonstrated that steady state was reached during the first BTDS 10 application. No significant difference in Cmin was observed across the three applications. Total and peak plasma buprenorphine exposures were similar after each of the seven-day administrations of BTDS.
  
  
  CONCLUSIONS
  Three consecutive once-weekly applications of BTDS 10 provided consistent and sustained delivery of buprenorphine. Steady-state plasma concentrations were reached within 48 hours of the first application of BTDS 10. Patch adhesion analysis confirmed the appropriateness of the seven-day application period. Overall, BTDS 10 was safe and well tolerated.
authors.affiliation: Purdue Pharma L.P., Stamford, Connecticut 06901, USA. Ram.Kapil@pharma.com
authors.forename: Ram P
authors.initials: RP
authors.lastname: Kapil
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cipriano
authors.forename: Kristen
authors.initials: K
authors.lastname: Friedman
authors.forename: Gregory
authors.initials: G
authors.lastname: Michels
authors.forename: Manjunath S
authors.initials: MS
authors.lastname: Shet
authors.forename: Salvatore V
authors.initials: SV
authors.lastname: Colucci
authors.forename: Glen
authors.initials: G
authors.lastname: Apseloff
authors.forename: Joseph
authors.initials: J
authors.lastname: Kitzmiller
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Harris
mesh_terms: D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D002047:Buprenorphine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008875:Middle Aged
chemical_list: D000701:Analgesics, Opioid; D002047:Buprenorphine