The Pharmacokinetics and Local Tolerability of a Novel Sublingual Formulation of Buprenorphine

Pain Med. 2019 Jan 1;20(1):143-152. doi: 10.1093/pm/pnx321.

Abstract

Aim: The principal study objective was to investigate the pharmacokinetic characteristics and determine the absolute bioavailability and tolerability of a new sublingual (SL) buprenorphine wafer.

Methods: The study was of open label, two-way randomized crossover design in 14 fasted healthy male and female volunteers. Each participant, under naltrexone block, received either a single intravenous dose of 300 mcg of buprenorphine as a constant infusion over five minutes or a sublingual dose of 800 mcg of buprenorphine in two treatment periods separated by a seven-day washout period. Blood sampling for plasma drug assay was taken on 16 occasions throughout a 48-hour period (predose and at 10, 20, 30, and 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 and 48 hours postdose). The pharmacokinetic parameters were determined by noncompartmental analyses of the buprenorphine plasma concentration-time profiles. Local tolerability was assessed using modified Likert scales.

Results: The absolute bioavailability of SL buprenorphine was 45.4% (95% confidence interval = 37.8-54.3%). The median times to peak plasma concentration were 10 minutes and 60 minutes after IV and SL administration, respectively. The peak plasma concentration was 2.65 ng/mL and 0.74 ng/mL after IV and SL administration, respectively. The half-lives were 9.1 hours and 11.2 hours after IV and SL administration, respectively. The wafer had very good local tolerability.

Conclusions: This novel sublingual buprenorphine wafer has high bioavailability and reduced Tmax compared with other SL tablet formulations of buprenorphine. The wafer displayed very good local tolerability. The results suggest that this novel buprenorphine wafer may provide enhanced clinical utility in the management of both acute and chronic pain.

Background: Buprenorphine is approved for use in pain management and opioid addiction. Sublingual administration of buprenorphine is a simple and noninvasive route of administration and has been available for many years. Improved sublingual formulations may lead to increased utilization of this useful drug for acute and chronic pain management.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Sublingual
  • Adolescent
  • Adult
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / therapeutic use*
  • Biological Availability
  • Buprenorphine / administration & dosage
  • Buprenorphine / pharmacokinetics*
  • Buprenorphine / therapeutic use*
  • Cross-Over Studies
  • Female
  • Humans
  • Male
  • Opioid-Related Disorders / drug therapy*
  • Pain Management / methods
  • Young Adult

Substances

  • Analgesics, Opioid
  • Buprenorphine