Clinical pharmacokinetics of oral buspirone in patients with impaired renal function.
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.
Caccia
S
S
Istituto di Ricerche Farmacologiche Mario Negri Via Eritrea, Milano.
Vigano
G L
GL
Mingardi
G
G
Garattini
S
S
Gammans
R E
RE
Placchi
M
M
Mayol
R F
RF
Pfeffer
M
M
D000284:Administration, Oral; D000328:Adult; D002065:Buspirone / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008875:Middle Aged
C037921:1-(2-pyrimidinyl)piperazine; D002065:Buspirone