Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

How do CYP2C19*2 and CYP2C19*17 genetic polymorphisms affect the efficacy and safety of diazepam in patients with alcohol withdrawal syndrome?

How do CYP2C19*2 and CYP2C19*17 genetic polymorphisms affect the efficacy and safety of diazepam... AbstractBackgroundDiazepam is one of the most commonly prescribed tranquilizers for therapy of alcohol withdrawal syndrome (AWS). Despite its popularity, there is currently no precise information on the effect of genetic polymorphisms on its efficacy and safety. The objective of our study was to investigate the effect of CYP2C19*2 and CYP2C19*17 genetic polymorphisms on the efficacy and safety of diazepam in patients with AWS.MethodsThe study was conducted on 30 Russian male patients suffering from the AWS who received diazepam in injections at a dosage of 30.0 mg/day for 5 days. The efficacy and safety assessment was performed using psychometric scales and scales for assessing the severity of adverse drug reactions.ResultsBased on the results of the study, we revealed the differences in the efficacy of therapy in patients with different CYP2C19 681G>A (CYP2C19*2, rs4244285) genotypes: (CYP2C19*1/*1) −8.5 [−15.0; −5.0], (CYP2C19*1/*2 and CYP2C19*2/*2) −12.0 [−13.0; −9.0], p = 0.021. The UKU scale scores, which were used to evaluate the safety of therapy, were also different: (CYP2C19*1/*1) 7.0 [6.0; 12.0], (CYP2C19*1/*2 and CYP2C19*2/*2) 9.5 [8.0; 11.0], p = 0.009. Patients carrying different CYP2C19 –806C>T (CYP2C19*17, rs12248560) genotypes also demonstrated differences in therapy efficacy and safety rates.ConclusionsThus, the effects of CYP2C19*2 and CYP2C19*17 genetic polymorphisms on the efficacy of diazepam were demonstrated. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Drug Metabolism and Drug Interactions de Gruyter

How do CYP2C19*2 and CYP2C19*17 genetic polymorphisms affect the efficacy and safety of diazepam in patients with alcohol withdrawal syndrome?

Download PDF
8 pages

Loading next page...
 
/lp/de-gruyter/how-do-cyp2c19-2-and-cyp2c19-17-genetic-polymorphisms-affect-the-tVR8Jr9ZG8

References

References for this paper are not available at this time. We will be adding them shortly, thank you for your patience.

Publisher
de Gruyter
Copyright
© 2020 Walter de Gruyter GmbH, Berlin/Boston
ISSN
2191-0162
eISSN
2363-8915
DOI
10.1515/dmpt-2019-0026
Publisher site
See Article on Publisher Site

Abstract

AbstractBackgroundDiazepam is one of the most commonly prescribed tranquilizers for therapy of alcohol withdrawal syndrome (AWS). Despite its popularity, there is currently no precise information on the effect of genetic polymorphisms on its efficacy and safety. The objective of our study was to investigate the effect of CYP2C19*2 and CYP2C19*17 genetic polymorphisms on the efficacy and safety of diazepam in patients with AWS.MethodsThe study was conducted on 30 Russian male patients suffering from the AWS who received diazepam in injections at a dosage of 30.0 mg/day for 5 days. The efficacy and safety assessment was performed using psychometric scales and scales for assessing the severity of adverse drug reactions.ResultsBased on the results of the study, we revealed the differences in the efficacy of therapy in patients with different CYP2C19 681G>A (CYP2C19*2, rs4244285) genotypes: (CYP2C19*1/*1) −8.5 [−15.0; −5.0], (CYP2C19*1/*2 and CYP2C19*2/*2) −12.0 [−13.0; −9.0], p = 0.021. The UKU scale scores, which were used to evaluate the safety of therapy, were also different: (CYP2C19*1/*1) 7.0 [6.0; 12.0], (CYP2C19*1/*2 and CYP2C19*2/*2) 9.5 [8.0; 11.0], p = 0.009. Patients carrying different CYP2C19 –806C>T (CYP2C19*17, rs12248560) genotypes also demonstrated differences in therapy efficacy and safety rates.ConclusionsThus, the effects of CYP2C19*2 and CYP2C19*17 genetic polymorphisms on the efficacy of diazepam were demonstrated.

Journal

Drug Metabolism and Drug Interactions – de Gruyter

Published: Mar 26, 2020

References

  • The UKU side effect rating scale. A new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients
  • The elimination of diazepam in Chinese subjects is dependent on the mephenytoin oxidation phenotype
  • Diazepam metabolism by human liver microsomes is mediated by both S-mephenytoin hydroxylase and CYP3A isoforms
  • Diazepam metabolism by cDNA-expressed human 2C P450s: identification of P4502C18 and P4502C19 as low K(M) diazepam N-demethylases
  • Extreme duration of diazepam-associated sedation in a patient with alcohol delirium and CYP2C19 polymorphisms
  • Complications of alcohol withdrawal: pathophysiological insights
  • The elimination of diazepam in Chinese subjects is dependent on the mephenytoin oxidation phenotype
  • The influence of CYP3A5 polymorphisms on haloperidol treatment in patients with alcohol addiction
  • Effect of early and focused benzodiazepine therapy on length of stay in severe alcohol withdrawal syndrome
  • Effect of common CYP3A4 and CYP3A5 variants on the pharmacokinetics of the cytochrome P450 3A phenotyping probe midazolam in cancer patients
  • Alcohol withdrawal: what is the benzodiazepine of choice?
  • Alcohol withdrawal syndromes in the intensive care unit
  • Genotyping and phenotyping of CYP2D6 and CYP3A isoenzymes in patients with alcohol use disorder: correlation with haloperidol plasma concentration
  • A strategy of escalating doses of benzodiazepines and phenobarbital administration reduces the need for mechanical ventilation in delirium tremens
  • Effects of genetic polymorphism of cytochrome P450 enzymes on the pharmacokinetics of benzodiazepines
  • The P450 oxidoreductase genotype is associated with CYP3A activity in vivo as measured by the midazolam phenotyping test
  • Alcohol withdrawal syndrome: benzodiazepines and beyond
  • Predictors of resistant alcohol withdrawal (RAW): a retrospective case-control study
  • Effects of genetic polymorphism of cytochrome P450 enzymes on the pharmacokinetics of benzodiazepines
  • The UKU side effect rating scale. A new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients
  • Classics in chemical neuroscience: diazepam (valium)
  • Extreme duration of diazepam-associated sedation in a patient with alcohol delirium and CYP2C19 polymorphisms
  • Diazepam in the treatment of moderate to severe alcohol withdrawal
  • Diazepam metabolism by human liver microsomes is mediated by both S-mephenytoin hydroxylase and CYP3A isoforms
  • Pharmacodynamic genetic polymorphisms affect adverse drug reactions of haloperidol in patients with alcohol-use disorder
  • Predictors of resistant alcohol withdrawal (RAW): a retrospective case-control study
  • Utilizing CIWA-Ar to assess use of benzodiazepines in patients vulnerable to alcohol withdrawal syndrome
  • Diazepam in the treatment of moderate to severe alcohol withdrawal
  • Effect of common CYP3A4 and CYP3A5 variants on the pharmacokinetics of the cytochrome P450 3A phenotyping probe midazolam in cancer patients
  • The influence of CYP3A5 polymorphisms on haloperidol treatment in patients with alcohol addiction
  • The P450 oxidoreductase genotype is associated with CYP3A activity in vivo as measured by the midazolam phenotyping test
  • Genotyping and phenotyping of CYP2D6 and CYP3A isoenzymes in patients with alcohol use disorder: correlation with haloperidol plasma concentration
  • Diazepam metabolism by cDNA-expressed human 2C P450s: identification of P4502C18 and P4502C19 as low K(M) diazepam N-demethylases
  • Role of CYP2C19 gene polymorphism in acute alcohol withdrawal treatment with loading dose of diazepam in a South Indian population
  • Alcohol withdrawal: what is the benzodiazepine of choice?
  • Pharmacodynamic genetic polymorphisms affect adverse drug reactions of haloperidol in patients with alcohol-use disorder
  • Complications of alcohol withdrawal: pathophysiological insights
  • Effect of early and focused benzodiazepine therapy on length of stay in severe alcohol withdrawal syndrome
  • Classics in chemical neuroscience: diazepam (valium)
  • Alcohol withdrawal syndrome: benzodiazepines and beyond
  • Pharmacokinetics and pharmacodynamics of etizolam are influenced by polymorphic CYP2C19 activity
  • Role of CYP2C19 gene polymorphism in acute alcohol withdrawal treatment with loading dose of diazepam in a South Indian population
  • Alcohol withdrawal syndromes in the intensive care unit
  • A strategy of escalating doses of benzodiazepines and phenobarbital administration reduces the need for mechanical ventilation in delirium tremens
  • Role of cDNA-expressed human cytochromes P450 in the metabolism of diazepam
  • Role of cDNA-expressed human cytochromes P450 in the metabolism of diazepam
  • Pharmacokinetics and pharmacodynamics of etizolam are influenced by polymorphic CYP2C19 activity
  • Utilizing CIWA-Ar to assess use of benzodiazepines in patients vulnerable to alcohol withdrawal syndrome