title: Bioavailability and kinetics of cibenzoline in patients with normal and impaired renal function.
abstract: To test the hypothesis that renal failure alters the disposition of cibenzoline in humans, an absolute bioavailability and elimination kinetic study was performed. We used the simultaneous administration of a stable isotope variant (SASIV). Eight healthy volunteers and eight matched hemodialysis patients each received simultaneously an 80-mg intravenous infusion of 15N-2-cibenzoline and a single 80-mg cibenzoline capsule. Cibenzoline plasma concentrations were assayed by a gas chromatographic-mass spectrometric assay. A compartment-independent kinetic analysis showed a plasma clearance of 707 mL/min and an elimination half-life of 7.3 hours after the intravenous dose in healthy volunteers. In renal-failure patients, cibenzoline clearance decreased to 224 mL/min and half-life increased to 22.4 hours. Decreased plasma clearance was due to decreases in both renal and nonrenal clearance. Absolute bioavailability was 83% and 90% in healthy volunteers and renal-failure patients, respectively. Hemodialysis accounted for only 13% of drug clearance.
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis.
authors.forename: G
authors.initials: G
authors.lastname: Aronoff
authors.forename: M
authors.initials: M
authors.lastname: Brier
authors.forename: M L
authors.initials: ML
authors.lastname: Mayer
authors.forename: M
authors.initials: M
authors.lastname: Barbalas
authors.forename: K
authors.initials: K
authors.lastname: Aogaichi
authors.forename: R
authors.initials: R
authors.lastname: Sloan
authors.forename: R
authors.initials: R
authors.lastname: Brazzell
authors.forename: J
authors.initials: J
authors.lastname: Massarella
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D006207:Half-Life; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D007668:Kidney / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000503:physiopathology; D008657:Metabolic Clearance Rate; D008875:Middle Aged
chemical_list: D007093:Imidazoles; C032151:cifenline