Mahmood I, Sahajwalla C
Division of Pharmaceutical Evaluation I, Food and Drug Administration, Rockville, Maryland, USA.
Clin Pharmacokinet. 1999 Apr;36(4):277-87. doi: 10.2165/00003088-199936040-00003.
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 20 mg, the drug is rapidly absorbed. The mean peak plasma concentration (Cmax) is approximately 2.5 micrograms/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 40 mg. 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 20 mg 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.
丁螺环酮是一种抗焦虑药物，给药剂量为15毫克/天。该药物的作用机制尚未完全明确，但其可能通过作用于中枢神经系统的多巴胺能系统或与5-羟色胺受体结合发挥作用。口服20毫克丁螺环酮后，药物迅速吸收。平均血浆峰浓度（Cmax）约为2.5微克/升，达峰时间在1小时以内。丁螺环酮的绝对生物利用度约为4%。丁螺环酮被广泛代谢。其主要代谢产物之一是1-嘧啶基哌嗪（1-PP），它可能对丁螺环酮的药理活性有贡献。丁螺环酮的分布容积为5.3升/千克，全身清除率约为1.7升/小时/千克，消除半衰期约为2.5小时，在10至40毫克的剂量范围内药代动力学呈线性。每日10毫克丁螺环酮多次给药9天后，母体化合物或代谢产物（1-PP）均无蓄积。与食物同服使丁螺环酮的Cmax和血浆浓度-时间曲线下面积（AUC）增加了2倍。单次服用20毫克剂量后，肾功能损害患者的Cmax和AUC与健康志愿者相比增加了2倍。肝功能损害患者相同剂量下的Cmax和AUC比健康个体高15倍。肝功能损害患者中丁螺环酮的半衰期是健康个体的两倍。丁螺环酮的药代动力学不受年龄或性别的影响。丁螺环酮与维拉帕米、地尔硫䓬、红霉素和伊曲康唑合用时，可使丁螺环酮的血浆浓度大幅升高，而西咪替丁和阿普唑仑的影响可忽略不计。利福平可使丁螺环酮的血浆浓度降低近10倍。
