rifampin and Opioid-Related-Disorders

The use of oral methadone in opioid substitution treatment (OST) for the management of opioid use disorder is established clinical practice. Confounding treatment is the increased risks of contracting Mycobacterium tuberculosis, the mainstay treatment of which incorporates the potent CYP 2B6 inducer rifampicin.. This study applied pharmacokinetic modelling using virtual clinical trials, to pharmacokinetically quantify the extent and impact of rifampicin-mediated drug-drug interactions (DDI) on methadone plasma concentrations. An R-methadone model was developed and validated against 11 retrospective clinical studies prior to use in all subsequent studies. The aims were to investigate: (i) the impact of the DDI on daily methadone doses of 60 mg, 90 mg and 120 mg; (ii) dose escalation during rifampicin and (iii) dose reduction following rifampicin cessation.. A dose increase to 160 mg daily during rifampicin treatment phases was required to maintain peak methadone plasma concentrations within a derived therapeutic window of 80-700 ng/mL. Dose escalation prior to rifampicin initiation was not required and resulted in an increase in subjects with supra-therapeutic concentrations. However, during rifampicin cessation, a dose reduction of 10 mg every 2 days commencing prior to rifampicin cessation, ensured that most patients possessed a peak methadone plasma concentration within an optimal therapeutic window.. Rifampicin significantly alters methadone plasma concentrations and necessitates dose adjustments. Daily doses of almost double those used perhaps more commonly in clinical practice are required for optimal plasma concentration and careful consideration of dose reduction strategies would be required during the deinduction phase.

Topics: Adult; Analgesics, Opioid; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Female; Humans; Male; Methadone; Middle Aged; Models, Biological; Nucleic Acid Synthesis Inhibitors; Opiate Substitution Treatment; Opioid-Related Disorders; Retrospective Studies; Rifampin

Topics: Antibiotics, Antitubercular; Drug Interactions; Humans; Methadone; Narcotics; Opioid-Related Disorders; Rifampin

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.. 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.. 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.. 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.

Topics: Adult; Antitubercular Agents; Buprenorphine; Drug Interactions; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Rifabutin; Rifampin; Substance Withdrawal Syndrome

The treatment of tuberculosis usually includes the antibiotic rifampicin, especially in patients with concomitant human immunodeficiency virus infection. Some of these patients are in withdrawal therapy for drug abuse. When opiate screening is carried out in patients receiving rifampicin, false positive results are detected with the kinetic interaction of microparticles in solution method. We evaluated this interference in a Cobas-Integra analyzer and found a 12% cross-reactivity of rifampicin for antibiotic concentrations ranging from 0.19 to 6.08 mumol/l (156 to 5000 micrograms/l). This effect is not explained by the colour of the rifampicin solutions. Calculations assuming first order kinetics of elimination show that more than 18 hours after a single oral dose of 600 mg of rifampicin, a false positive result for opiates could be obtained. This indicates that the risk of a false positive result must always be considered when urine samples from these patients are analyzed.

Topics: AIDS-Related Opportunistic Infections; Antibiotics, Antitubercular; False Positive Reactions; Female; Humans; Immunoassay; Male; Microspheres; Narcotics; Opioid-Related Disorders; Rifampin; Tuberculosis, Pulmonary

Topics: Adult; Antibiotics, Antitubercular; Female; Humans; Methadone; Opioid-Related Disorders; Rifampin; Substance Withdrawal Syndrome; Tuberculosis, Pulmonary

Morphine and its derivatives are metabolized by the liver microsomal enzyme system with a high first-pass effect after oral application. In four of 44 HIV-infected i.v. drug abusers who participated in a levomethadon maintenance program, we observed sustained symptoms of under-dosage and loss of effect of there to fore well-tolerated substitution therapy during rifampin treatment or therapy with zidovudine or fucidic acid. As a pharmacological model substance for cytochrome p 450 enzymes, measurement of antipyrine in serum by high pressure liquid chromatography revealed induction of cytochrome p 450 isoenzymes. The half-life of antipyrine decreased (patient 1 from 11.3 to 8.4 h and patient 2 from 10.7 to 7.6 h after rifampin, patient 3 from 12.2 to 8.6 h after fucidic acid, and patient 4 from 10.6 to 8.6 h after zidovudine). In i.v. drug abusers on levomethadon maintenance programs, adjustment of the levomethadon dosage may be necessary when specific therapy for HIV infection and associated diseases requires the use of drugs known to be potent inducers of the liver microsomal enzyme system.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Female; Fusidic Acid; Humans; Male; Methadone; Opioid-Related Disorders; Opportunistic Infections; Prospective Studies; Rifampin; Stereoisomerism; Substance Abuse, Intravenous; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Adult; Female; Humans; Male; Methadone; Mycobacterium avium-intracellulare Infection; Opioid-Related Disorders; Rifampin; Substance Abuse, Intravenous; Substance Withdrawal Syndrome

The results are reported of a service in Hong Kong of intensive antituberculosis chemotherapy with 5 drugs given daily for 4 months, or until discharge from hospital or release from prison if earlier, in the treatment of male Chinese drug addicts and prisoners who had pulmonary tuberculosis positive for acid-fast bacilli on microscopic examination of the sputum. Of 69 patients who received 4 months of chemotherapy, all those with sputum cultures negative for M. tuberculois initially, and more than 80% of those with positive cultures, 41% of whom had strains resistant to isoniazid, streptomycin, or both drugs, achieved quiescent disease, which was maintained for a year of follow-up. Some of the patients who received less than 4 months of chemotherapy also reponded well. Despite the 5 drugs, the frequency of adverse reactions to the regimen was low.

Topics: Antitubercular Agents; Drug Administration Schedule; Drug Resistance, Microbial; Ethambutol; Heroin Dependence; Hong Kong; Humans; Isoniazid; Male; Opioid-Related Disorders; Opium; Prisoners; Pyrazinamide; Rifampin; Streptomycin; Tuberculosis; Tuberculosis, Pulmonary