Abstract
1 A series of studies has 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 food 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.
Keywords: nicardipine, biotransformation, pharmacokinetics, human subjects
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Selected References
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