INFLUENCE OF AGE, RENAL AND LIVER IMPAIRMENT ON THE PHARMACOKINETICS OF RISPERIDONE IN MAN

被引:96
作者
SNOECK, E
VANPEER, A
SACK, M
HORTON, M
MANNENS, G
WOESTENBORGHS, R
MEIBACH, R
HEYKANTS, J
机构
[1] CLIN RES CTR,AUSTIN,TX
[2] JANSSEN RES FDN,DEPT CLIN RES,TITUSVILLE,NJ
关键词
RISPERIDONE; PHARMACOKINETICS; ELDERLY; RENAL DISEASE; LIVER DISEASE;
D O I
10.1007/BF02246543
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The pharmacokinetics of the antipsychotic agent risperidone were investigated in healthy young and elderly subjects, cirrhotic patients and patients with moderate and severe renal insufficiency. In a comparative trial, a single oral 1-mg dose was administered to fasting subjects. Plasma and urine concentrations of the parent compound risperidone and the active moiety (i.e. risperidone plus 9-hydroxy-risperidone) were measured by radioimmunoassays. No or only small changes in plasma protein binding were observed in hepatic and renal disease, whereas the protein binding was not influenced by aging. The inter-individual variability in plasma concentrations of the active moiety was much less than the variability in plasma concentrations of risperidone. Three out of six subjects, behaving like poor metabolizers, were on medication (thiethylperazine, amitriptyline, metoprolol) that may inhibit risperidone metabolism by CYP2D6 (debrisoquine 4-hydroxylase). The pharmacokinetics of risperidone in elderly and cirrhotic patients were comparable to those in young subjects, whereas total oral clearance was reduced in renal disease patients. The elimination rate and clearance of 9-hydroxy-risperidone was reduced in elderly and renal disease patients because of a diminished creatinine clearance. The CL(oral) of the active moiety, which is primarily 9-hydroxy-risperidone, was reduced by about 30% in the elderly and by about 50% in renal disease patients. In addition, the t(1/2) of the active moiety was prolonged (19 h in young subjects versus about 25 h in elderly and renal disease patients). Based upon the pharmacokinetics of the active moiety, a dose reduction and a cautious dose titration is advised in the elderly and in patients with renal disease. In cirrhotic patients, the single-dose pharmacokinetics were comparable to those in healthy young subjects.
引用
收藏
页码:223 / 229
页数:7
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