A review of the human metabolism and pharmacokinetics of nicardipine hydrochloride

1. A series of studies have been conducted to investigate the disposition of nicardipine following oral and intravenous administration to human subjects. 2. Nicardipine is rapidly absorbed, rapidly and extensively metabolised and rapidly eliminated from plasma. 3. Nicardipine is subject to extensive pre-systemic elimination. This is partially saturable by increasing dose or duration of dosing. 4. Because of nicardipine's saturable pre-systemic elimination, steady-state plasma levels and bioavailability show a non-linear relationship with dose over the range 10 to 40 mg three times daily. 5. On repeated oral administration steady-state levels are apparently achieved within 3 days without subsequent change. This is consistent with the measured terminal elimination half-life of 11.8 h, and a demonstrated absence of effect on hepatic microsomal enzyme systems. 6. Consumption of blood before nicardipine administration reduces its bioavailability. 7. Studies in the elderly have demonstrated that increased hypotensive effects with age cannot be attributed to pharmacokinetic changes. 8. Studies in renally impaired subjects have demonstrated that dosage at the lower end of the recommended range is appropriate.