R-verapamil: pharmacokinetics and effects on PR interval, blood pressure and heart rate

1. This study in healthy normotensive male volunteers investigated the pharmacokinetics and the effects on electrocardiographic PR interval, blood pressure and heart rate of single oral doses of the single isomer R-verapamil (250, 500 and 1000 mg) in comparison to placebo and 240 mg racemic verapamil. 2. After 500 and 1000 mg R-verapamil there were significant prolongations in PR interval, maximal at 1-2 h after dosing and coincident with peak plasma drug concentrations, but these were not significantly different from the maximum prolongation obtained with 240 mg racemic verapamil. 3. After 1000 mg R-verapamil there was a significant hypotensive effect, particularly on standing. 4. Single doses of 500 and 1000 mg R-verapamil produced peak plasma drug concentrations in the range 1000-3000 ng ml-1. If this concentration range is appropriate for adjuvant cancer chemotherapy it can be predicted that similar steady state concentrations will occur with a dosage regimen of 300 mg 3 times daily.