Influence of time of administration on verapamil pharmacokinetics.

The plasma concentration-time profile of verapamil was studied in eight healthy drug-free volunteers after oral administration of a single 80 mg dose of the drug on six separate occasions at different times of day (4 AM, 8 AM, noon, 4 PM, 8 PM, and midnight). The median maximum plasma concentration of verapamil was significantly higher after the 8 AM and noon administrations (p less than 0.05) than at any other time. The median area under the concentration-time curve was also significantly higher (p less than 0.05) after administration at 8 AM and noon than at other times. The median time to maximum concentration was not significantly different at any time point (p greater than 0.05). It is possible that concentration-related adverse effects of verapamil could be avoided by choosing the time of day when the drug is prescribed. This concept may also apply to other drugs that have circadian effects in their pharmacokinetic profiles.