NCT01854489

Effects of Rifampicin on the Pharmacokinetics and Pharmacodynamics of Sublingual and Intravenous Buprenorphine

Effects of Rifampicin on the Pharmacokinetics and Pharmacodynamics of Sublingual and Intravenous Buprenorphine: A Four-phase Cross-over Study in Healthy Subjects.

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: Turku University Hospital · Other Government
• Sex: All
• Age: 18 Years – 40 Years
• Healthy volunteers: Accepted

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.

Conditions

• Healthy

Interventions

Type	Name	Description
DRUG	Placebo	The volunteers will be given Oral placebo at 20.00 for 7 days \[Phase 1 \]
DRUG	Rifampicin	The volunteers will be given oral rifampicin (Rimapen, Orion, Finland) 600 mg as a single daily dose at 20.00 for 7 days
DRUG	Buprenorphine	The volunteers will be given single dose of 0,4 mg intra venous buprenorphine or 0,6 mg sublingual buprenorphine on day 5.

Timeline

• Start date: 2013-04-01
• Primary completion: 2014-11-01
• Completion: 2014-11-01
• First posted: 2013-05-15
• Last updated: 2014-11-20

Locations

1 site across 1 country: Finland