Effects of Rifampicin on the Pharmacokinetics and Pharmacodynamics of Sublingual and Intravenous Buprenorphine
Condition: Healthy
Study type: Interventional
Phase: Phase 4

Summary: 
      This study is aimed to examine the possible interactions of sublingual and intravenous
      buprenorphine with rifampicin.
    

Detailed description: 
      Variability in drug response can be due to either pharmacokinetic or pharmacodynamic factors.
      The reasons why people differ in pharmacokinetics or pharmacodynamics are manifold and
      include, e.g., genetic factors, diseases, age and concomitantly administered drugs. Oxidation
      reactions are dominant in the metabolism of drugs and cytochrome P-450 enzymes (CYP) have
      been recognized as chief contributors. We have previously shown that drug interactions
      mediated by the inhibition of CYP enzymes may be of major clinical significance.Buprenorphine
      is a semisynthetic partial µ-opioid receptor agonist. In low doses, it is used in the
      treatment of moderate acute and chronic pain whereas in high doses, it is used in the
      management of opioid withdrawal symptoms and opioid addiction. It has high affinity for the
      µ-opioid receptor and its analgesic efficacy is 20-40 times that of morphine. It acts as an
      antagonist at the myy-opioid receptor and as an agonist at the myy-opioid receptor and
      opioid-like receptor (ORL-1).

      Buprenorphine undergoes extensive first-pass metabolism and has low oral bioavailability of
      15 %. Bioavailability following sublingual administration of buprenorphine is higher, 50-60
      %. After high sublingual doses of buprenorphine (8-24 mg), peak plasma concentrations are
      reached in 1 hour and after low sublingual doses (0.4 mg) they are reached in approximately 3
      h. Approximately two-thirds of a buprenorphine dose is excreted unchanged, and the rest is
      metabolized in the liver and intestinal wall. N-dealkylation of buprenorphine mainly via
      CYP3A but also CYP2C8 yields norbuprenorphine, and glucuronidation yields
      buprenorphine-3-glucuronide. Norbuprenorphine is excreted in the urine after subsequent
      conjugation. 80-90 % of buprenorphine is excreted by the biliary system and enterohepatic
      circulation.Although few interaction studies of high-dose buprenorphine and antiretrovirals
      have been conducted, the effect of CYP3A inducers on the pharmacokinetics of low-dose
      buprenorphine is unknown. Because the use of buprenorphine in pain management is increasing
      after the introduction of transdermal buprenorphin patches to the market, it is clinically
      relevant to study and quantify possible interactions of buprenorphine with inducers of its
      CYP3A-mediated metabolism such as rifampicin.
    

Intervention name(s): Placebo; Rifampicin; Buprenorphine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): The volunteers will be given Oral placebo at 20.00 for 7 days [Phase 1 ]; The volunteers will be given oral rifampicin (Rimapen, Orion, Finland) 600 mg as a single daily dose at 20.00 for 7 days; The volunteers will be given single dose of 0,4 mg intra venous buprenorphine or 0,6 mg sublingual buprenorphine on day 5.
Other intervention name(s): Temgesic 0,2 mg resoriblet; Temgesic 0,3 mg/ml
Intervention MeSH terms: Rifampin; Buprenorphine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Basic Science
Keywords: Buprenorphine; Rifampicin; Interactions; Pharmakokinetics; Pharmakodynamics