Clinical Pharmacokinetics of Oral Buspirone in Patients with Impaired Renal Function

Abstract

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.

Disposition kinetics of buspirone in patients with renal or hepatic impairment after administration of single and multiple doses

“…Single-dose pharmacokinetics of buspirone have been investigated in patients with renal [6] or hepatic [7] impairment. The study in patients with renal failure [6] indicated that the apparent clearance ofbuspirone and 1-PP in anuric patients was approximately one-third of that in normal subjects, and that there was no significant relationship between creatinine clearance and apparent buspirone clearance. The single-dose and steady-state pharmacokinetic data from the present study confirmed that the disposition of buspirone was not related to the degree of renal impairment.…”

“…Buspirone clearance in patients with renal impairment was approximately a third to a half of that in normal volunteers [6]. However, in a single-dose pharmacokinetic study in patients with hepatic impairment, a 16-fold increase in plasma level and a significant increase in the half-life of buspirone were reported in cirrhotic patients compared to healthy subjects [7].…”

“…Since hepatic biotransformation is the major elimination pathway of buspirone, repeated administration of buspirone may result in significant accumulation of the intact drug and its metabolites due to the possibility of altered disposition in patients with impaired hepatic function. Although urinary excretion of buspirone accounts for less than 1% of the administered dose, clearance of buspirone and 1-PP is decreased in patients with moderate to severe renal impairment [6]. Delineation of steady-state pharmacokinetics of buspirone in patients with renal or hepatic impairment is necessary to investigate the extent of accumulation of buspirone and 1-PP, and to develop safe and effective dosage regimens in these patients.…”

A trial of buspirone for the control of disruptive behaviors in community‐dwelling patients with dementia

“…More specifically, successful buspirone use has been reported in two case studies of dementia patients with disruptive behaviors (Tiller et al, 1988;Colenda, 1988). In addition, buspirone offers several advantages over neuroleptics and benzodiazepines for use in the elderly, including the absence of adverse effect on motor performance and cognitive function, an advantageous side-effect profile, and predictable pharmacokinetics and metabolism (Newton et al, 1982;Smiley and Moskowitz, 1986;Newton et af., 1986;Hart et af., 1991;Lucki et al, 1987;Robinson et al, 1988;Bohm et al, 1990;Gammans et al, 1989;Caccia et al, 1988).…”

Psychotherapeutic Agents in End‐Stage Renal Disease

“…Buspirone is extensively metabolized by the liver to various metabolites including 1‐prymidinyl‐piperazine (1‐PP), which has approximately 1/20th the anxiolytic activity of buspirone. 1‐PP AUC and half‐life were significantly higher in anuric HD patients compared to healthy controls . Although HD significantly reduced 1‐PP AUC, 1‐PP AUC was still greater than in healthy subjects.…”