Influence of CYP3A activity on the level of equilibrium concentration bromodydrochlorophenyl benzodyazephine (Phenazepam®) in patients with anxiety disorders, comorbid with alcoholic dependence
Background. The use of benzodiazepine anxiolytics series in drug treatment practice is to base the treatment of alcohol withdrawal syndrome. Bromdihydrochlorphenylbenzodiazepine (Phenazepam®) is often used in the Russian Federation to relieve symptoms of severe, maladaptive anxiety in combination with sleep disorders in patients with alcohol withdrawal syndrome. At the same time, the use of such an effective remedy requires a doctor to competently assess the situation, taking into account the possibility of undesirable drug reactions, control over the development of anxiety disorder in patients with alcohol dependence and timely withdrawal of the drug. This requires a more complete understanding of the pharmacokinetics of Phenazepam®, in the study of the influence of polymorphism of genes encoding proteins of transport and biotransformation influence the rate of elimination Phenazepam®, its effectiveness and safety. Method. This study was conducted on 94 Russian patients suffering from alcohol dependence. Patients for the treatment of anxiety disorder for 5 days received bromdigidrohlorfenilbenzodiazepine (Phenazepam®) in tablet form in an average dosage of 4.0 mg/day. For determining the activity of CYP3A was investigated concentration in urine is the relationship of the concentrations of the endogenous substrate of this isoenzyme and its metabolite (6-beta-hydroxycortisol / cortisol) by high-performance liquid chromatography with mass spectrometry (HPLC with MS/MS). Therapeutic drug monitoring of Phenazepam® was evaluated by the level of its equilibrium concentration in plasma using high-performance liquid chromatography with mass spectrometry (HPLC with MS/MS). Result. Revealed a statistically significant relationship between the level of equilibrium concentration of Phenazepam®, and the activity of CYP3A, and in turn confirms that the effectiveness, safety and occurrence of adverse drug reactions in therapy with phenazepam® depends on CYP3A gene polymorphism.