title: Pharmacokinetics of fluvastatin in subjects with renal impairment and nephrotic syndrome.
abstract: The pharmacokinetics (PK) and safety of fluvastatin, a hydroxymethylglutaryl-coenzyme A reductase inhibitor, were assessed in subjects with renal impairment and nephrotic syndrome. In a single-center, open-label, parallel-group study, a single dose of fluvastatin 40 mg was administered to subjects (8 per group, n = 48) with nephrotic syndrome (group II), healthy subjects (group I), and subjects with various degrees of renal impairment (groups III to VI). Subjects undergoing hemodialysis received two doses, one 2 days before and one just prior to hemodialysis. Blood samples to determine the PK parameters of fluvastatin were collected from 0 to 12 hours after drug intake. Noncompartmental PK evaluation and statistical analysis (descriptive and ANOVA) were performed. Safety was evaluated and vital signs were monitored. There was no difference in the PK parameters AUC0-infinity and Cmax of fluvastatin between healthy subjects and subjects with renal impairment. Fluvastatin was not removed from plasma by hemodialysis. In patients with nephrotic syndrome, the values for AUC0-infinity and Cmax were less than half of those obtained in the other groups; terminal half-life values, however, were comparable. Fluvastatin was well tolerated in all study participants. Only few adverse events of mild to moderate intensity were reported. There were no clinically relevant changes in laboratory parameters in the subjects with renal impairment. Renal impairment did not affect the PK of fluvastatin after a single oral dose. Exposure to fluvastatin was lower in subjects with nephrotic syndrome. Fluvastatin also was well tolerated in subjects with nephrotic syndrome.
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Appel-Dingemanse
authors.forename: T
authors.initials: T
authors.lastname: Smith
authors.forename: M
authors.initials: M
authors.lastname: Merz
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D005229:Fatty Acids, Monounsaturated / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007211:Indoles / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000097:blood* / Q000188:drug therapy; D006435:Renal Dialysis / Q000706:statistics & numerical data; D051437:Renal Insufficiency / Q000097:blood* / Q000188:drug therapy
chemical_list: D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D000077340:Fluvastatin