Abstract
Buspirone is an anxiolytic drug given at a dosage of 15 mg/day. The mechanism of action of the drug is not well characterised, but it may exert its effect by acting on the dopaminergic system in the central nervous system or by binding to serotonin (5-hydroxytryptamine) receptors. Following a oral dose of buspirone 20mg, the drug is rapidly absorbed. The mean peak plasma concentration (Cmax) is approximately 2.5 μg/L, and the time to reach the peak is under 1 hour. The absolute bioavailability of buspirone is approximately 4%.
Buspirone is extensively metabolised. One of the major metabolites of buspirone is 1-pyrimidinylpiperazine (1-PP), which may contribute to the pharmacological 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 pharmacokinetics 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). Administration with food increased the Cmax and area under the plasma concentration-time curve (AUC) of buspirone 2-fold.
After a single 20mg dose, the Cmax and AUC increased 2-fold in patients with renal impairment as compared with healthy volunteers. The Cmax and AUC were 15-fold higher for the same dose in patients with hepatic impairment compared with healthy individuals. The half-life of buspirone in patients with hepatic impairment was twice that in healthy individuals. The pharmacokinetics of buspirone were not affected by age or gender.
Coadministration of buspirone with verapamil, diltiazem, erythromycin and itraconazole substantially increased the plasma concentration of buspirone, whereas Cimetidine and alprazolam had negligible effects. Rifampicin (rifampin) decreased the plasma concentrations of buspirone almost 10-fold.
Similar content being viewed by others
References
Riblet LA, Eison SA, Eison MS, et al. Neuropharmacology of buspirone. Psychopharmacology 1984; 17 Suppl. 3: 69–78.
Temple DL, Yevich JP, New JS. Buspirone: chemical profile of a new class of anxioselective agents. J Clin Psychiatry 1982; 43: 4–9.
Cimino M, Ponzio F, Achilli G, et al. Dopaminergic effects of buspirone, a novel anxiolytic agent. Biochem Pharmacol 1983; 32: 1069–74.
Glaser T, Traber J. Buspirone: action on serotonin receptors in calf hippocampus. Eur J Pharmacol 1983; 88: 137–8.
Berlin I, Chalon S, Payan C, et al. Evaluation of the α2-adrenoceptor blocking properties of buspirone and ipsapirone in healthy subjects: relationship with the plasma concentration of the common metabolite 1-(2-pyrimidinyl)piperazine. Br J Clin Pharmacol 1995; 39: 243–9.
Oakley NR, Jones BJ. Buspirone enhances [3H]flunitrazepam binding in vivo. Eur J Pharmacol 1983; 87: 499–500.
Kristjansson F. Sensitive determination of buspirone in serum by solid phase extraction and two dimensional high performance liquid chromatography. J Chromatogr 1991; 566: 250–6.
Tsai TH, Chen CF. Measurement and pharmacokinetic analysis of buspirone by means of brain microdialysis coupled to high performance liquid chromatography with electrochemical detection. J Chromatogr 1997; 762: 269–73.
Bianchi G, Caccia S. Simultaneous determination of buspirone, gepirone, ipsapirone and their common metabolite 1-(2-pyrimidinyl)piperazine in rat plasma and brain by high performance liquid chromatography. J Chromatogr 1988; 431: 477–80.
Odontiadis J, Franklin M. Simultaneous quantitation of buspirone and its major metabolite 1-(2-pyrimidinyl)piperazine in human plasma by high performance liquid chromatography with coulometric detection. J Pharm Biomed Anal 1996; 14: 347–51.
Sciacca MA, Duncan GF, Shea JP, et al. Simultaneous quantitation of buspirone and 1-(2-pyrimidinyl)piperazine in human plasma and urine by capillary gas chromatography mass spectrometry. J Chromatogr 1988; 428: 265–74.
Gaillard Y, Gay Montchamp JP, Ollagnier M. Simultaneous screening and quantitation of alpidem, Zolpidem, buspirone and benzodiazepines by dual channel gas chromatography using electron capture and nitrogen phosphorus detection after solid phase extraction. J Chromatogr 1993; 622: 97–208.
Betto P, Meneguz A, Ricciarello G, et al. Simultaneous high performance liquid chromatographic analysis of buspirone and its metabolite 1-(2 pyrimidinyl)-piperazine in plasma using electrochemical detection. J Chromatogr 1992; 575: 17–21.
Kerns EH, Bullen WW, Gammans RE. Quantitative analysis of 1-(2-pyrimidinyl)piperazine in plasma by capillary gas chromatography mass spectrometry. J Chromatogr 1986; 377: 195–203.
Gammans RE, Kerns EH, Bullen WW. Capillary gas chromatographic mass spectrometric determination of buspirone in plasma. J Chromatogr 1985; 345: 285–97.
Goldthwaite Jr CA, Hsieh FY, Womble SW, et al. Liquid chromatography/chemical reaction interface mass spectrometry as an alternative to radioisotopes for quantitative drug metabolism studies. Anal Chem 1996; 68: 2996–3001.
Mayol RF, Adamson DS, Gammans RE, et al. Pharmacokinetics and disposition of 14C-buspirone HCl after intravenous and oral dosing in man [abstract]. Clin Pharmacol Ther 1985; 37: 210.
Jajoo HK, Mayol RF, LaBudde JA, et al. Metabolism of the antianxiety drug buspirone in human subjects. Drug Metab Disp 1989; 17: 634–40.
Gammans RE, Mayol RF, Eison ME. Concentration of buspirone and 1-pyrimidinylpiperazine, a metabolite in rat brain [abstract]. Fed Proc 1983; 42: 377.
Bullen WW, Bivens DL, Gammans RE, et al. The binding of buspirone to human plasma proteins [abstract]. Fed Proc 1985; 44: 1123.
Gammans RE, Mayol RF, Mackenthun AV, et al. The relationship between buspirone bioavailability and dose in healthy subjects. Biopharm Drug Disp 1985; 6: 139–45.
Barbhaiya RH, Shukla UA, Pfeffer M, et al. Disposition kinetics of buspirone in patients with renal or hepatic impairment after administration of single and multiple doses. Eur J Clin Pharmacol 1994; 46: 41–7.
Mayol RF, Gammans RE, Mackenthun AV, Sokya LF. The effect of food on the bioavailability of buspirone HCl [abstract]. Clin Res 1983; 31: 631A.
Caccia S, Vigano GL, Mingardi G, et al. Clinical pharmacokinetics of oral buspirone in patients with impaired renal function. Clin Pharmacokinet 1988; 14: 171–7.
Dalhoff K, Poulsen HE, Garred P, et al. Buspirone pharmacokinetics in patients with cirrhosis. Br J Clin Pharmacol 1987; 24: 547–50.
Gammans RE, Mayol RF, LaBudde JA. Metabolism and disposition of buspirone. Am J Med 1986; 80 Suppl. 3B: 41–51.
Lamberg TS, Kivisto KT, Neuvonen PJ. Effects of verapamil and diltiazem on the pharmacokinetics and pharmacodynamics of buspirone. Clin Pharmacol Ther 1998; 63: 640–5.
Kivisto KT, Lamberg TS, Kantola T, et al. Plasma buspirone concentrations are greatly increased by erythromycin and itraconazole. Clin Pharmacol Ther 1997; 62: 348–54.
Erwin CW, Linnoila M, Hartwell J, et al. Effects of buspirone and diazepam, alone and in combination with alcohol, on skilled performance and evoked potentials. J Clin Psychopharmacol 1986; 6: 199–209.
Ashton CH, Rawlins MD, Tyrer SP. A double blind placebo controlled study of buspirone in diazepam withdrawal in chronic benzodiazepine users. Br J Psychiatry 1990; 157: 232–8.
van Laar MW, Volkerts ER, van Willigenburg AR Therapeutic effects and effects on actual driving performance of chronically administered buspirone and diazepam in anxious outpatients. J Clin Psychopharmacol 1992; 12: 86–95.
Gammans RE, Pfeffer M, Westrick ML, et al. Lack of interaction between Cimetidine and buspirone. Pharmacotherapy 1987; 7: 72–9.
Ciraulo DA, Barnhill JG, Ciraulo AM, et al. Alterations in pharmacodynamics of anxiolytics in abstinent alcoholic men: subjective responses, abuse liability, and electroencephalographic effects of alprazolam, diazepam, and buspirone. J Clin Pharmacol 1997; 37: 64–73.
Lamberg TS, Kivisto KT, Neuvonen PJ. Concentrations and effects of buspirone are considerably reduced by rifampicin. Br J Clin Pharmacol 1998; 45: 381–5.
Buch AB, Van Harken DR, Seidehamel RJ, et al. A study of pharmacokinetic interaction between buspirone and alprazolam at steady state. J Clin Pharmacol 1993; 33: 1104–9.
Huang HF, Jann MW, Wei FC, et al. Lack of pharmacokinetic interaction between buspirone and haloperidol in patients with schizophrenia. J Clin Pharmacol 1996; 36: 963–9.
Olkkhola VA, Neuvonen PJ. Diltiazem enhances the effects of triazolam by inhibiting its metabolism. Clin Pharmacol Ther 1996; 59: 369–75.
Backman JT, Olkkola KT, Aranko K, et al. Dose of midazolam should be reduced during diltiazem and verapamil treatments. Br J Clin Pharmacol 1994; 37: 221–5.
Schlanz KD, Myre SA, Bottorff MB. Pharmacokinetic interactions with calcium channel antagonists: Part I. Clin Pharmacokinet 1991; 21: 344–56.
Schlanz KD, Myre SA, Bottorff MB. Pharmacokinetic interactions with calcium channel antagonists: Part II. Clin Pharmacokinet 1991; 21: 448–60.
Lilja JJ, Kivisto KT, Backman JT, et al. Grapefruit juice substantially increases plasma concentrations of buspirone. Clin Pharmacol Ther 1998; 64: 655–60.
Kolars JC, Schmiedline-Ren P, Schuetz JD, et al. Identification of rifampicin-induced P450IIIA (CYP3A4) in human small bowel enterocytes. J Clin Invest 1992; 90: 1871–8.
Dawson GW, Jue SG, Brogden RN. Alprazolam: a review of its pharmacodynamic properties and efficacy in the treatment of anxiety and depression. Drugs 1984; 11: 132–47.
Sethy VH, Harris DW. Determination of biological activity of alprazolam, triazolam and their metabolites. J Pharm Pharmacol 1982; 34: 115–6.
Desmond PV, Patwardhan RW, Schenkar S, et al. Cimetidine impairs elimination of chlordiazepoxide in man. Ann Intern Med 1980; 93: 266–8.
Klotz U, Reimann I. Delayed clearance of diazepam due to Cimetidine. N Engl J Med 1980; 302: 1012–4.
Goff DC, Midha KK, Brotman AW, et al. An open trial of buspirone added to neuroleptics in schizophrenic patients. J Clin Psychopharmacol 1991; 11: 193–7.
Kivisto KT, Lamberg TS, Neuvonen PJ. Interactions of buspirone with itraconazole and rifampicin: effects on the pharmacokinetics of the active 1-(2-pyrimidinyl)-piperazine metabolite of buspirone. Pharmacol Toxicol 1999; 84: 94–7.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mahmood, I., Sahajwalla, C. Clinical Pharmacokinetics and Pharmacodynamics of Buspirone, an Anxiolytic Drug. Clin Pharmacokinet 36, 277–287 (1999). https://doi.org/10.2165/00003088-199936040-00003
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003088-199936040-00003