Liver buprenorphine

Ibrahim RB, Wilson JG, Thorsby ME, et al Effect of buprenorphine on CYP3Aactivity in rat and human liver microsomes. Life Sci 66 1293—1298, 2000 Iguchi MY, Handelsman L, Bickel WK, et al Benzodiazepine and sedative use/abuse by methadone maintenance clients. Drug Alcohol Depend 32 257—266, 1993 Isbell H Manifestations and treatment of addiction to narcotic drugs and barbiturates. Med Clin North Am 34 423 38, 1950... 

Buprenorphine is metabolized by the liver mediated by cytochrome P450 3A4, and its clearance is related to hepatic blood flow. Plasma protein binding is about 96%. The mean elimination half-life from plasma is 37 hours. 

An excellent brief article on buprenorphine treatment has been provided by Taikato et al. (2005), which notes the common possible side-effects (headaches, nausea and vomiting, sweating, constipation, etc.) and drug interactions. The limited central depressant effect of buprenorphine may be compounded by alcohol and antidepressants, while the metabolism of buprenorphine can be enhanced by anticonvulsants, with therefore possibly reduced efficacy. There have been some case reports of liver toxicity from buprenorphine that is reversible if the medication is stopped (Herve et al. 2004), and often clinical guidelines will recommend that liver function tests are included in buprenorphine treatment, as they definitely should be with naltrexone. 

Droblem. In comparison with other opioids, buprenorphine appears to have a very Buprenorphine is almost completely metabolised in the liver by A/-dealkylaion... 

Although buprenorphine [byou preh NOR feen] is classified as a partial agonist acting at the p receptor, it behaves like morphine in naive patients. However, it can also antagonize morphine. Buprenorphine is administered parenterally and has a long duration of action because of its tight binding to the receptor. It is metabolized by the liver and excreted in the bile and urine. Adverse effects include respiratory depression, decrease (or, rarely, increase) in blood pressure, nausea and dizziness. 

With increasing use of buprenorphine in the treatment of opioid dependence, it has been confirmed that the use of buprenorphine in opioid-dependent individuals with a history of hepatitis causes significant increases in aspartate transaminase and alanine transaminase activities (9). Liver enzymes should be monitored before giving buprenorphine to patients with hepatitis. 

Petty NM, Bickel WK, Piasecki D, Marsch LA, Badger GJ. Elevated liver ettzyme levels in opioid-dependent patients with hepatitis treated with buprenorphine. Am J Addict 2000 9(3) 265-9. 

In an in vitro stndy of the effects of the HIV-1 protease inhibitors, ritonavir, indinavir, and saquinavir, which are metabolized by the liver CYP3A4, all three protease inhibitors inhibited methadone demethylation and buprenorphine dealkylation in rank order of potency ritonavir > indinavir > saquinavir (35). Clinical studies are required to establish the further relevance of these observations. 

Buprinorphine is a semisynthetic opioid analgesic derived from thebaine. It binds readily to the opioid receptors in the CNS but dissociates from them slowly, which may be responsible for its long duration of action. Buprenorphine (0.3 mg DVt) exerts its analgesic actions in 15 minutes and has a duration of action of 6 hours. It is bound to plasma proteins to the extent of 96%, is metabolized in the liver to a certain extent (N-dealkylmetabolite), and is excreted unchanged in the feces. Buprenorphine causes respiratory depression and elevates cerebrospinal pressure (contraindicated in head injury or conditions where intracranial pressure may be high). 

Iribame C, Picart D, Creano Y, Bail JP, Berthou F. Involvement of c3ftochrome P450 3A4 in N-dealkylation of buprenorphine in human liver microsomes. Life Sci (1997) 60,1953-64. 

Ibrahim RB, Wilson JG, Thorsby ME, Edwards DJ. Effect of buprenorphine on CYP3A activity in rat and human liver microsornes. Life Sci (2000) 66,12S8-8. 

Chang Y, Moody DE. Effect of benzodiazepines on die metabolism of buprenorphine in human liver microsomes. EurJ Clin Pharmacol (2005) 60, 875-81. 

Fluoxetine inhibits the activity of the cytochrome P450 isoenzyme CYP2D6 within the liver so that the metabolism of oxycodone to an aetive metabolite oxymorphone is reduced. The metabolism of hydroeodone and similar opioids may also be affected by CYP2D6 inhibitors, see Opioids Codeine and related drugs + Quinidine , p.l84. Buprenorphine and morphine are not metabolised by CYP2D6, so their metabolism would not be expeeted to be affected by fluoxetine. Buprenorphine is metabolised by CYP3A4 and so fluvoxamine might be expected to inhibit its metabolism to some extent. 

Buprenorphine is metabolized to an active JV-dealkyl ated metabolite, norbuprenorphine. Norbu-prenorphine has one-fourth the potency of buprenorphine. It is metabolized in the liver and the gut. It is seen that the excretion of buprenorphine is not affected by the presence of end-stage renal failure. 

Buprenorphine is metabolized in the liver by CYP3A4 and N-dealkylated to form norbuprenorphine. It is also conjugated with glucuronic acid to form buprenorphine-3P-0-glucuronide and norbuprenor-phine-3P-0-glucuronide. Approximately 2/3 of buprenorphine is eliminated unchanged in feces [1-3]. 

Liver Therapeutic doses of buprenorphine have been linked to acute hepatitis and renal failure [185 ]. 

The authors highlighted the need for liver function monitoring in the first few weeks of buprenorphine treatment in susceptible patients, such as those with hepatitis, alcohol abuse, or concomitant use of drugs that cause mitochondrial toxicity. 

Zuin M, Giorgini A, Selmi C, Battezzati PM, Cocchi CA, Crosignani A, Benetti A, Invemizzi P, Podda M. Acute liver and renal failure during treatment with buprenorphine at therapeutic dose. Dig Liver Dis 2009 41(7) e8-10. 

Severe pain Fentanyl (mostly cleared VAS 7-10 by the liver inactive metabolites) Buprenorphine (with dose adjustment according to residual renal function mostly cleared by the liver inactive metabolites) Methadone (mostly cleared by the liver inactive metabolites)... 

LIVER A long-term study of patients with hepatitis C who were randomised to buprenorphine versus methadone for long-term pain control did not show any adverse elevation to transaminases over a 4-week period [85 -]. The combination product buprenorphine/naloxone, however, was associated with an elevated aminotransferase in 25/150 (17%) HIV-negative patients over 4 weeks in a different study [86 ]. 

Saxon A], ling W, EBUhouse M, Thomas C, Hasson A, Ang A, et al. Buprenorphine/Naloxone and methadone effects on laboratory indices of liver health a randomized trial. Drug Alcohol Depend February 1,2013 128(l-2) 71-6. 

M. Zuin, A. Giorgini, C. Selmi, P. M. Battezzati, C. A. Cocchi, A. Crosignani, A. Benetti, P. Invernizzi and M. Podda, Acute liver and renal failure during treatment with buprenorphine at the therapeutic dose. Dig. Liver Dis., 2009, 41, c8-el0. 

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