Buspirone pharmacokinetics and molecular data

Pharmacokinetics
Mechanism Absorption Food Nonlinear pharmacokinetics Protein binding Metabolism Elimination half-life

Mechanism
The mechanism of action of Buspirone is unknown. Buspirone differs from typical benzodiazepine anxiolytics in that it does not exert anticonvulsant or muscle relaxant effects. It also lacks the prominent sedative effect that is associated with more typical anxiolytics. In vitro preclinical studies have shown that Buspirone has a high affinity for serotonin (5-HT1A) receptors. Buspirone has no significant affinity for benzodiazepine receptors and does not affect GABA binding in vitro or in vivo when tested in preclinical models. Buspirone has moderate affinity for brain D2-dopamine receptors. Some studies do suggest that Buspirone may have indirect effects on other neurotransmitter systems. Return to top

Absorption
Buspirone is rapidly absorbed in man and undergoes extensive first-pass metabolism. In a radiolabeled study, unchanged Buspirone in the plasma accounted for only about 1% of the radioactivity in the plasma. Following oral administration, plasma concentrations of unchanged Buspirone are very low and variable between subjects. Peak plasma levels of 1 to 6 ng/mL have been observed 40 to 90 minutes after single oral doses of 20 mg. The single-dose bioavailability of unchanged Buspirone when taken as a tablet is on the average about 90% of an equivalent dose of solution, but there is large variability. Return to top

Food
The effects of food upon the bioavailability of Buspirone have been studied in eight subjects. They were given a 20 mg dose with and without food; the area under the plasma concentration-time curve (AUC) and peak plasma concentration (Cmax) of unchanged Buspirone increased by 84% and 116% respectively, but the total amount of Buspirone immunoreactive material did not change. This suggests that food may decrease the extent of presystemic clearance of Buspirone. Return to top

Nonlinear pharmacokinetics
A multiple-dose study conducted in 15 subjects suggests that Buspirone has nonlinear pharmacokinetics. Thus, dose increases and repeated dosing may lead to somewhat higher blood levels of unchanged Buspirone than would be predicted from results of single-dose studies. Return to top

Protein binding
An in vitro protein binding study indicated that approximately 86% of Buspirone is bound to plasma proteins. It was also observed that aspirin increased the plasma levels of free Buspirone by 23%, while flurazepam decreased the plasma levels of free Buspirone by 20%. However, it is not known whether these drugs cause similar effects on plasma levels of free Buspirone in vivo, or whether such changes, if they do occur, cause clinically significant differences in treatment outcome. An in vitro study indicated that Buspirone did not displace highly protein-bound drugs such as phenytoin, warfarin, and propranolol from plasma protein, and that Buspirone may displace digoxin. Return to top

Metabolism
Buspirone is metabolized primarily by oxidation, which in vitro has been shown to be mediated by cytochrome P450 3A4 (CYP3A4). Several hydroxylated derivatives and a pharmacologically active metabolite, 1-pyrimidinylpiperazine (1-PP), are produced. Return to top

Elimination half-life
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; fecal excretion accounted for 18% to 38% of the dose. The average elimination half-life of unchanged Buspirone after single doses of 10 to 40 mg is about 2 to 3 hours. Return to top