Caccia S, Vigano G L, Mingardi G, Garattini S, Gammans R E, Placchi M, Mayol R F, Pfeffer M
Istituto di Ricerche Farmacologiche Mario Negri Via Eritrea, Milano.
Clin Pharmacokinet. 1988 Mar;14(3):171-7. doi: 10.2165/00003088-198814030-00005.
12 patients with mild to moderate impairment of renal function and 12 healthy subjects each received 20mg buspirone as a single dose in this acute study. Six anuric patients with chronic renal failure were given two 20mg doses of buspirone, the first 2 days before haemodialysis (between dialyses) and the second during hemodialysis (2 hours before dialysis began). The differences between the median pharmacokinetic values of buspirone for healthy subjects, patients with mild to moderate renal impairment, and anuric patients were not statistically significant. Similarly, there were no significant differences between values in mild to moderate renal failure vs healthy subjects. Some of the median pharmacokinetic values for the active buspirone metabolite 1-(2-pyrimidinyl)-piperazine (1-PP), however, differed significantly for anuric patients, compared with healthy subjects or patients with mild to moderate renal impairment. When assessed between and during haemodialysis, the anuric patients had significantly (p less than 0.05) greater pharmacokinetic median values: half-life (t 1/2) = 15.2 vs 9.8 hours; area under the concentration-time curve (AUC) = 604 vs 404 nmol/L.h; and mean residence time (MRT) = 9.28 vs 6.96 hours. No firm recommendation for specific dosage can be made based on the present data. However, it does appear that in patients with mild to moderate renal impairment, the pharmacokinetics of buspirone and its active metabolite 1-PP are similar to those in individuals with normal renal function. For anuric patients higher concentrations of the 1-PP metabolite are attained while they are not undergoing haemodialysis. A dosage reduction of 25 to 50% might be necessary when buspirone is given to anuric patients.
在这项急性研究中,12例肾功能轻度至中度受损的患者和12名健康受试者均接受了20mg丁螺环酮单次给药。6例慢性肾衰竭的无尿患者接受了两剂20mg的丁螺环酮,第一剂在血液透析前2天(透析间期)服用,第二剂在血液透析期间(透析开始前2小时)服用。丁螺环酮在健康受试者、轻度至中度肾功能受损患者和无尿患者中的中位药代动力学值差异无统计学意义。同样,轻度至中度肾衰竭患者与健康受试者的值之间也无显著差异。然而,活性丁螺环酮代谢物1-(2-嘧啶基)-哌嗪(1-PP)的一些中位药代动力学值,无尿患者与健康受试者或轻度至中度肾功能受损患者相比有显著差异。在血液透析期间及透析后评估时,无尿患者的药代动力学中位值显著更高(p小于0.05):半衰期(t 1/2)=15.2小时对9.8小时;浓度-时间曲线下面积(AUC)=604对404nmol/L·h;平均驻留时间(MRT)=9.28对6.96小时。基于目前的数据无法给出具体剂量的明确建议。然而,轻度至中度肾功能受损患者中,丁螺环酮及其活性代谢物1-PP的药代动力学似乎与肾功能正常的个体相似。对于无尿患者,在未进行血液透析时1-PP代谢物会达到更高浓度。给无尿患者服用丁螺环酮时可能需要减少25%至50%的剂量。