Steady-state pharmacokinetics of fluvastatin in healthy subjects following a new extended release fluvastatin tablet, Lescol® XL

This was an open-label, randomized, three-period, three-treatment, multiple dose, crossover study in 12 healthy male and female subjects. This study evaluated single dose and steady-state pharmacokinetics of fluvastatin following single and multiple dose administrations of a new extended release fluvastatin 8 h matrix tablet, Lescol(R) XL 80 mg and 160 mg doses once a day. The study also included a twice a day administration of an immediate release (IR) form of fluvastatin capsule, Lescol(R), for comparative purposes. All doses were administered for 7 days. The safety and tolerability were also assessed. The pharmacokinetics of fluvastatin were evaluated on days 1 and 7 following each treatment. Fluvastatin systemic exposure was 50% less when administered as Lescol(R) XL 80 mg qd compared with Lescol(R) IR 40 mg bid. Conversely, fluvastatin systemic exposure was 22% higher when administered as Lescol(R) XL 160 mg qd compared with Lesco(R) IR 40 mg bid. Single doses of Lescol(R) XL 80 mg and 160 mg were dose proportional but, deviation (30%) from dose proportionality was observed for the Lescol(R) XL 160 mg at steady-state. There appeared to be moderate (20%-40%) accumulation of serum fluvastatin maximal concentrations and exposure after multiple doses of Lescol(R) XL tablets. Both Lescol(R) XL 80 mg and 160 mg showed delayed absorption and longer apparent elimination half-life compared with fluvastatin IR capsule. Single and multiple doses of fluvastatin were generally well tolerated in this healthy volunteer population. Adverse event profiles were consistent with the published safety profile of the marketed formulations. Aside from one incidence of creatine phosphokinase (CPK) elevation (following Lescol(R) XL 160 mg qd treatment), there were no safety concerns with any of the treatments when administered acutely (7 days). Copyright (C) 2004 John Wiley Sons, Ltd.