The anxiolytic (tranquilizing) agent of the non-benzodiazepine series also has an antidepressant effect. Unlike classical anxiolytics, it does not have antiepileptic, sedative, hypnotic and muscle relaxant effects.
The mechanism of action is associated with the effect of buspirone on the serotonergic and dopaminergic systems. Selectively blocks presynaptic dopamine receptors and increases the rate of excitation of dopamine neurons in the midbrain. In addition, buspirone is a selective partial agonist of 5-HT1A-serotonin receptors. Buspirone does not have a significant effect on benzodiazepine receptors and does not affect the binding of GABA, does not have a negative effect on psychomotor functions, does not cause tolerance, drug dependence and withdrawal syndrome. Does not potentiate the effect of alcohol. By anxiolytic activity, buspirone is approximately equal to benzodiazepines.
The therapeutic effect develops gradually and is noted after 7-14 days from the start of treatment, the maximum effect is recorded after 4 weeks.
After oral administration, buspirone is rapidly and almost completely absorbed from the gastrointestinal tract.
Buspirone undergoes intensive first-pass metabolism through the liver. Therefore, an unchanged substance is found in the systemic circulation in a small concentration, which has significant individual differences. Bioavailability is 4%. Cmax in blood plasma is achieved 60–90 minutes after taking the drug. In healthy volunteers, buspirone had a linear (dose-proportional) pharmacokinetics after taking 10–40 mg. Similar pharmacokinetic parameters were found in elderly patients. After a single ingestion of 20 mg of the drug, its plasma levels range from 1 to 6 ng / ml. Approximately 95% of buspirone is bound to plasma proteins (86% is bound to plasma albumin, the rest is α1acidic glycoprotein).
Buspirone undergoes oxidative metabolism, mainly with the participation of CYP3A4 isoenzymes. Various hydroxylated metabolites are formed. The main metabolite - (5-OH-buspirone) is inactive. The dealkylated metabolite - (1- (2-pyrimidinyl) piperazine, 1-PP) is active. Its anxiolytic activity is 4–5 times lower than that of the original substance, but its level in the blood plasma is higher, and T1/2 about 2 times longer than that of buspirone. After a single injection 14C-labeled buspirone, 29–63% of radioactivity is excreted in the urine within 24 hours, mainly in the form of metabolites. Approximately 18–38% of the administered dose is excreted in the feces. After a single dose of 10–40 mg T1/2 the initial substance is about 2–3 hours, and T1/2 active metabolite is 4.8 hours.
Simultaneous food intake slows down the absorption of buspirone, but due to the decrease in pre-system clearance (first-pass effect), the bioavailability of buspirone is significantly increased. After ingestion, the AUC value of buspirone is increased by 84%, and its Cmax - by 16%.
Css blood plasma can be reached approximately 2 days after the start of regular intake.
Seeming vd is 5.3 l / kg.
Buspirone is excreted in breast milk, but there are no data on placental transmission.
Elevated plasma buspirone levels and AUC values, as well as T prolongation1/2 may occur in violation of the liver. In connection with the release of an unchanged substance in bile, a second peak of buspirone concentration in the blood plasma is possible. Patients with cirrhosis of the liver should be prescribed the drug in lower doses or in the same doses with extended intervals.
In renal failure, clearance of buspirone can be reduced by 50%. In case of renal insufficiency, buspirone should be administered with caution and in reduced doses.
The pharmacokinetics of buspirone in elderly patients is not changed.
1 tablet contains:
active substance: buspirone hydrochloride 10 mg,
Excipients: lactose monohydrate 111.4 mg; MCC; sodium carboxymethyl starch; magnesium stearate; silicon dioxide colloidal anhydrous
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