Brand Name: Buspar
Generic Name: Buspirone

Buspirone is a psychotropic drug with selective anxiolytic properties which belongs chemically to the class of compounds known as the azaspirodecanediones, not chemically or pharmacologically related to benzodiazepines, barbiturates, or other known psychotropic agents.

Buspirone shares some of the properties of the benzodiazepines and the neuroleptics, as well as demonstrating other pharmacological action. Buspirone attenuates punishment suppressed behavior in animals and exerts a taming effect, but is devoid of anticonvulsant and muscle relaxant properties and does not bind to the benzodiazepine/GABA receptor complex. Buspirone affects a variety of dopamine mediated biochemical and behavioral events, but is free of cataleptic activity. Buspirone has an affinity for brain D2-dopamine receptors, where it acts as an antagonist and agonist, and for the 5-HT1A receptors, where it acts as an agonist. Buspirone does not block the neuronal reuptake of monoamines and, on chronic administration, it does not lead to changes in receptor density in the models investigated. However, the mechanism of action of buspirone remains to be fully elucidated.

Buspirone is rapidly absorbed in man and undergoes extensive first pass metabolism. Following oral administration, low peak plasma levels of unchanged drug, of 1 to 6 ng/mL were observed 40 to 90 minutes after a single 20 mg dose. In a number of studies performed in healthy volunteers, the mean half-life of buspirone ranged from 2 to 3 hours up to approximately 11 hours with considerable variation in individual values. Multiple dose studies suggest that steady-state plasma levels were usually achieved within a few days. Buspirone is metabolized primarily by oxidation, which in vitro has been shown to be mediated by cytochrome P450 3A4 (CYP3A4) (see Precautions, Drug Interactions), producing several hydroxylated derivatives and a pharmacologically active metabolite, 1-pyrimidinylpiperazine (1-PP). In animal models predictive of anxiolytic potential, 1-PP has about 25% or less of the activity of buspirone. Peak plasma levels of 1-PP have been found to be higher than those of its parent drug and its half-life to be approximately double that of unchanged buspirone. In a single dose study using 14C labeled buspirone, 29 to 63% of the dose was excreted in the urine within 24 hours, primarily as metabolites, while fecal excretion accounted for 18 to 38% of the dose. In man, approximately 95% of buspirone is plasma protein bound. Other highly bound drugs, e.g., phenytoin, propranolol and warfarin, are not displaced by buspirone from plasma protein binding in vitro at clinically relevant concentrations. However, in vitro binding studies show that buspirone does displace digoxin.

The effects of food upon the bioavailability of buspirone tablets have been studied in 8 subjects. They were given a 20 mg dose with or without food. The AUC and Cmax of unchanged buspirone increased by 84% and 116%, respectively. The total amount of buspirone immunoreactive material did not change. This suggests that food may decrease the extent of presystemic clearance of buspirone.

Buspirone had no effect on hepatic microsomal enzyme activity when administered to rats for 5 days. In man, the effect of buspirone on drug metabolism or concomitant drug disposition has not been studied. Buspirone clearance is reduced in patients with hepatic impairment as well as in patients with impaired renal function. No significant differences in buspirone pharmacokinetics as a function of age and/or sex was found.