buprenorphine and Liver-Neoplasms

Buprenorphine, pentazocine, and naloxone are opioid drugs used for the treatment of pain and opioid dependence or overdose. Sulfation as catalyzed by the cytosolic sulfotransferases (SULTs) is involved in the metabolism of a variety of xenobiotics including drug compounds. Sulfation of opioid drugs has not been well investigated. The current study was designed to examine the sulfation of three opioid drugs, buprenorphine, pentazocine, and naloxone, in HepG2 human hepatoma cells and to identify the human SULT(s) responsible for their sulfation. Analysis of the spent media of HepG2 cells, metabolically labeled with [(35)S]sulfate in the presence of each of the three opioid drugs, showed the generation and release of their [(35)S]sulfated derivatives. A systematic analysis using eleven known human SULTs revealed SULT1A3 and SULT2A1 as the major responsible SULTs for the sulfation of, respectively, pentazocine and buprenorphine; whereas three other SULTs, SULT1A1, SULT1A2, and SULT1C4, were capable of sulfating naloxone. Enzymatic assays using combinations of these opioid drugs as substrates showed significant inhibitory effects in the sulfation of buprenorphine and pentazocine by naloxone. Differential sulfating activities toward the three opioid drugs were detected in cytosol or S9 fractions of human lung, liver, kidney, and small intestine. Collectively, these results imply that sulfation may play a role in the metabolism of buprenorphine, pentazocine, and naloxone in vivo.

Topics: Analgesics, Opioid; Buprenorphine; Carcinoma, Hepatocellular; Cytosol; Hep G2 Cells; Humans; Liver Neoplasms; Naloxone; Narcotic Antagonists; Pentazocine; Sulfates; Sulfotransferases

Severe pruritus is a frequent complication of cholestasis. Both serotonin and opioids play an important role in the development of this symptom. Guidelines to provide rational management of pruritus of cholestasis do not exist. We describe a patient with complex and malignant course of pruritus. She responded to several measures proposed (among other naltrexone), but rapidly became tolerant to them. Buprenorphine with an ultra low dose of naloxone was able to control her symptoms without development of tolerance until her death.

Topics: Aged; Buprenorphine; Cholestasis; Colonic Neoplasms; Drug Therapy, Combination; Fatal Outcome; Female; Humans; Liver Neoplasms; Naloxone; Narcotic Antagonists; Pruritus

Ten patients who underwent surgery (5 right hepatectomy and 5 colectomy) for cancer participated in a clinical controlled study. They were treated with buprenorphine (i.v. slow infusion) to relieve postsurgical pain. We found an increased urinary excretion of this drug in patients who underwent hepatectomy as compared with patients who underwent colectomy. However no differences in the occurrence of side-effects and/or in the therapeutic effect were observed between the two groups. We conclude that buprenorphine can be effectively and safely used also in patients with a resection of liver parenchyma.

Topics: Adenocarcinoma; Adult; Aged; Buprenorphine; Colectomy; Female; Hepatectomy; Humans; Liver Neoplasms; Male; Middle Aged; Pain, Postoperative

Postoperative pain relief with epidural morphine and buprenorphine was studied in 33 patients following hepatectomy. Morphine 2mg or buprenorphine 0.06mg in 10ml of normal saline was administered through an epidural catheter inserted at the Th10-11 or L3-4 interspace. Morphine injected at the lumbar level, as well as that injected at the thoracic level produced excellent and long-lasting (20.8 +/- 8.6 hours) pain relief. Respiratory rate decreased significantly following epidural morphine at the L3-4, but PaCO2 did not change. Buprenorphine injected at the thoracic level produced good and long-lasting (22.6 +/- 9.9 hours) pain relief, although buprenorphine injected at the lumbar level produced incomplete analgesia. The epidural administration of morphine 2mg at L3-4 or buprenorphine 0.06mg at Th10-11 may be recommended for postoperative analgesia following hepatectomy.

Topics: Adult; Aged; Analgesia, Epidural; Buprenorphine; Female; Hepatectomy; Humans; Injections, Epidural; Liver Neoplasms; Male; Middle Aged; Morphine; Pain, Postoperative