title: Rifampin, but not rifabutin, may produce opiate withdrawal in buprenorphine-maintained patients.
abstract: BACKGROUND
  This series of studies examines the pharmacokinetic/pharmacodynamic interactions between buprenorphine, an opioid partial agonist increasingly used in treatment of opioid dependence, and rifampin, a medication used as a first line treatment for tuberculosis; or rifabutin, an alternative antituberculosis medication.
  
  
  METHODS
  Opioid-dependent individuals on stable doses of buprenorphine/naloxone underwent two, 24-h blood sampling studies: (1) for buprenorphine pharmacokinetics and (2) following 15 days of rifampin 600 mg daily or rifabutin 300 mg daily for buprenorphine and rifampin or rifabutin pharmacokinetics.
  
  
  RESULTS
  Rifampin administration produced significant reduction in plasma buprenorphine concentrations (70% reduction in mean area under the curve (AUC); p=<0.001) and onset of opiate withdrawal symptoms in 50% of participants (p=0.02). While rifabutin administration to buprenorphine-maintained subjects resulted in a significant decrease in buprenorphine plasma concentrations (35% decrease in AUC; p<0.001) no opiate withdrawal was seen. Compared with historical control data, buprenorphine had no significant effect on rifampin pharmacokinetics, but was associated with 22% lower rifabutin mean AUC (p=0.009), although rifabutin and its active metabolite concentrations remained in the therapeutic range.
  
  
  CONCLUSIONS
  Rifampin is a more potent inducer of buprenorphine metabolism than rifabutin with pharmacokinetic and pharmacodynamic adverse consequences. Those patients requiring rifampin treatment for tuberculosis and receiving buprenorphine therapy are likely to require an increase in buprenorphine dose to prevent withdrawal symptoms. Rifabutin administration was associated with decreases in buprenorphine plasma concentrations, but no clinically significant adverse events were observed.
authors: University of California San Francisco, San Francisco, CA 94110, USA. elinore.mccance-katz@ucsf.edu
authors: Elinore F
authors: EF
authors: McCance-Katz
authors: David E
authors: DE
authors: Moody
authors: Sudha
authors: S
authors: Prathikanti
authors: Gerald
authors: G
authors: Friedland
authors: Petrie M
authors: PM
authors: Rainey
references: MMWR Recomm Rep. 1998 Oct 30;47(RR-20):1-58
references: 9809743
references: Anesthesiology. 2008 Mar;108(3):363-74
references: 18292673
references: Drug Alcohol Depend. 1996 Dec 2;43(1-2):71-7
references: 8957145
references: Drug Alcohol Depend. 2007 Dec 1;91(2-3):269-78
references: 17643869
references: J Acquir Immune Defic Syndr. 2010 Dec;55 Suppl 1:S37-42
references: 21045598
references: J Pharm Sci. 2009 Dec;98(12):4928-40
references: 19370547
references: Antimicrob Agents Chemother. 2010 Oct;54(10):4440-5
references: 20660678
references: J Addict Dis. 2005;24(3):49-59
references: 16186082
references: Basic Clin Pharmacol Toxicol. 2011 Jan;108(1):55-62
references: 20825389
references: Anal Biochem. 2002 Jul 1;306(1):31-9
references: 12069411
references: Br J Clin Pharmacol. 1999 Aug;48(2):168-79
references: 10417493
references: Ther Drug Monit. 2006 Apr;28(2):245-51
references: 16628138
references: Harv Rev Psychiatry. 2004 Nov-Dec;12(6):321-38
references: 15764468
references: Klin Wochenschr. 1985 Dec 2;63(23):1205-11
references: 4087830
references: Am J Addict. 2010 Jan-Feb;19(1):38-46
references: 20132120
references: J Psychiatr Res. 1975 Nov;12(3):189-98
references: 1202204
references: MMWR Morb Mortal Wkly Rep. 2000 Mar 10;49(9):185-9
references: 11795500
references: Drug Metab Lett. 2009 Apr;3(2):101-7
references: 19601871
references: J Psychoactive Drugs. 2003 Apr-Jun;35(2):253-9
references: 12924748
references: Clin Pharmacokinet. 2003;42(9):819-50
references: 12882588
references: Int J Tuberc Lung Dis. 2001 Jan;5(1):59-64
references: 11263518
references: Chem Res Toxicol. 1996 Mar;9(2):365-73
references: 8839037
references: Life Sci. 1997;60(22):1953-64
references: 9180349
references: J Antimicrob Chemother. 1996 Jun;37(6):1111-9
references: 8836814
references: Lancet. 2010 Jul 31;376(9738):367-87
references: 20650518
references: Antimicrob Agents Chemother. 1989 Aug;33(8):1237-41
references: 2552902
references: Clin Infect Dis. 2003 Aug 15;37(4):476-82
references: 12905130
references: Curr Opin Infect Dis. 2009 Feb;22(1):11-7
references: 19532076
references: J Psychoactive Drugs. 2006 Jun;38(2):203-5
references: 16903459
references: Drug Metab Dispos. 2006 Mar;34(3):440-8
references: 16381669
references: Am J Addict. 2010 Jan-Feb;19(1):4-16
references: 20132117
references: Clin Pharmacokinet. 2001;40(5):327-41
references: 11432536
references: Clin Pharmacol Ther. 2002 Nov;72(5):524-35
references: 12426516
references: Drug Metab Dispos. 1984 Sep-Oct;12(5):577-81
references: 6149907
references: Pharmacol Res. 1995 Oct;32(4):177-87
references: 8866833
references: N Engl J Med. 1976 May 13;294(20):1104-6
references: 1256526
references: Basic Clin Pharmacol Toxicol. 2009 Sep;105(3):211-5
references: 19500085
references: Clin Infect Dis. 2005 Jul 1;41 Suppl 1:S89-95
references: 16265622
references: Clin Infect Dis. 2006 Dec 15;43 Suppl 4:S224-34
references: 17109309
references: Drugs. 1994 Jun;47(6):983-1009
references: 7521834
references: Addiction. 1998 Apr;93(4):549-59
references: 9684393