Clinical pharmacokinetics and pharmacodynamics of buspirone, an anxiolyticdrug

Buspirone is an anxiolytic drug given at a dosage of 15 mg/day, The mechani sm of action of the drug is not well characterised, but it may exert its ef fect by acting on the dopaminergic system in the central nervous system or by binding to serotonin (5-hydroxytryptamine) receptors. Following a oral d ose of buspirone 20mg, the drug is rapidly absorbed. The mean peak plasma c oncentration (C-max) is approximately 2.5 mu g/L, and the time to reach the peak is under 1 hour. The absolute bioavailability of buspirone is approxi mately 4%. Buspirone is extensively metabolised. One of the major metabolites of buspi rone is 1-pyrimidinylpiperazine (1-PP), which may contribute to the pharmac ological activity of buspirone. Buspirone has a volume of distribution of 5.3 L/kg, a systemic clearance of about 1.7 L/h/kg. an elimination half-life of about 2.5 hours and the phar macokinetics are linear over the dose range 10 to 40mg. After multiple-dose administration of buspirone 10 mg/day for 9 days, there was no accumulation of either parent compound or metabolite (1-PP). Admini stration with food increased the Cma,and area under the plasma concentratio n-time curve (AUC) of buspirone 2-fold. After a single 20mg dose, the C-max and AUC increased 2-fold in patients wi th renal impairment as compared with healthy volunteers. The C-max and AUC were 15-fold higher for the same dose in patients with hepatic impairment c ompared with healthy individuals. The half-lift: of buspirone in patients w ith hepatic impairment was twice that in healthy individuals, The pharmacok inetics of buspirone were not affected by age or gender. Coadministration of buspirone with verapamil, diltiazem, erythromycin and I traconazole substantially increased the plasma concentration of buspirone, whereas cimetidine and alprazolam had negligible effects. Rifampicin (rifam pin) decreased the plasma concentrations of buspirone almost 10-fold.