Lack of Interaction between Modified-Release Fluvastatin and Amlodipine in Healthy Subjects

Design: This was a single-centre, six-sequence, three-period, randomised, crossover design study. Fluvastatin XL 80mg tablet and amlodipine 5mg tablet were administered once a day for 2 weeks either alone or in combination. Fluvastatin and amlodipine serum concentration profiles were characterised on day 14 for each treatment. The pharmacokinetic interaction between the two drugs was evaluated based on the p-values and 90% confidence intervals (CIs) for log-transformed highest observed concentration (C_max), area under the plasma concentration-time curve calculated by the linear trapezoidal method up to 24 hours (AUC₂₄), and apparent oral clearance at steady state (CL/F), using a single entity as the reference treatment and the combination as the test treatment. Adverse events (AEs), safety laboratory tests and physical examinations were evaluated for safety.

Results: The coadministration of fluvastatin XL and amlodipine resulted in no significant changes in the steady-state AUC (469 vs 454 μg · h/L), Cmax (96 vs 89 μg/L), and CL/F (197 vs 232 L/h) of fluvastatin when compared with fluvastatin XL alone. The p-values for these comparisons were between 0.172 and 0.238, and the 90% CIs for the geometric means were within 78% and 139%. A similar comparison for amlodipine showed no significant difference in the steady-state AUC (132 vs 140 μg· h/L), C_max (7.1 vs 7.5 μg/L) and CL/F (41 vs 40 L/h) of amlodipine. The p-values for these comparisons were between 0.309 and 0.353, and the 90% CIs for the geometric means were within 90% and 111%. The majority of the AEs were mild in severity. There were no clinically relevant changes in clinical laboratory results, physical examinations or vital sign parameters.