Pharmacokinetics of sustained-release verapamil after a single administration and at steady state

Summary

Pharmacokinetics of conventional 80 mg tablets and two types of sustained-release (SR) tablets containing 120 and 200 mg of verapamil were compared cross-over in 12 healthy volunteers. Serum concentrations of verapamil and norverapamil were analyzed both after a single oral dose and at steady state after t.i.d. administration of conventional tablets and b.i.d. administration of SR tablets. After 120 mg SR tablets serum concentrations of verapamil usually remained below 100 ng/ml for 5 days. This inadequate bioavailability was caused by very slow absorption. The relative bioavailability of verapamil in 200 mg SR tablets was 93–96% as compared to the conventional tablets. After 200 mg × 2 and 80 mg × 3 , the peak serum levels were about 300 and 190 ng/ml, respectively and the trough levels 123–153 and 52–56 ng/ml, respectively. The verapamil/norverapamil ratio varied from 0.69 to 0.84 after a single dose and from 0.8 to 0.93 at steady-state. By the 4th days of treatment, the accumulation ratios ranged between 1.75–2.07 and 1.30–1.75 for verapamil and norverapamil, respectively. For each preparation studied, the apparent Cl₁₀₁ of verapamil was significantly reduced at steady-state. These results show that 200 mg SR verapamil tablets fulfill the basic requirements of retard preparations allowing for twice or even once daily administration.