ISSN:
1432-1041
Keywords:
Key words Sertindole
;
Renal impairment; pharmacoki netics
;
hemodialysis
;
schizophrenia
;
antipsychotics
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
,
Medicine
Notes:
Abstract Objective: To study the effect of renal impairment on the pharmacokinetics of sertindole. Methods: A single 4 mg oral dose of sertindole was given to normal subjects ( n = 6) and subjects with various degrees of impaired renal function ( n = 18) classified into mild, moderate, and severe/hemodialysis based on their creatinine clearance). The relationships between the pharmacokinetic parameters and the degree of renal impairment were investigated using regression analysis with creatinine clearance as an explanatory variable along with body weight. Subjects were also genotyped for CYP2D6-A or 2D6-B mutations. Results: The mean CL/f and t1/2 values of sertindole ranged from 14 to 31 l · h−1 and from 73 to 93 h, respectively, and were not significantly related to creatinine clearances. There was no indication of any influence of creatinine clearance on the fraction of sertindole (0.994–0.995) binding to plasma proteins. The total fraction of the sertindole dose removed by dialysis was less than 0.1%. Subjects with B/B genotype ( n = 2) for CYP2D6 were associated with a distinctly lower clearance of sertindole (6.3 vs 25.3 l · h−1) than subjects with wt/wt genotype for CYP2D6. Conclusions: Since the pharmacokinetics of sertindole are unchanged by renal impairment, dosage adjustment does not appear to be necessary for subjects with various degrees of renal insufficiency or subjects with renal failure requiring hemodialysis.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s002280050278
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