Nimodipine

Nimodipine is a calcium channel blocker. The contractile processes of smooth muscle cells are dependent upon calcium ions, which enter these cells during depolarization as slow ionic transmembrane currents. Nimodipine inhibits calcium ion transfer into these cells and thus inhibits contractions of vascular smooth muscle. Nimodipine had a greater effect on cerebral arteries than on arteries elsewhere in the body, perhaps because it is highly lipophilic, allowing it to cross the blood-brain barrier; concentrations of Nimodipine as high as 12.5 ng/mL have been detected in the cerebrospinal fluid of Nimodipine-treated subarachnoid hemorrhage (SAH) patients. The precise mechanism of action of Nimodipine in SAH in humans is unknown. Clinical studies demonstrates a favorable effect of Nimodipine on the severity of neurological deficits caused by cerebral vasospasm following SAH, there is no arteriographic evidence that the drug either prevents or relieves the spasm of these arteries.Nimodipine is rapidly absorbed after oral administration, and peak concentrations are generally attained within one hour. The terminal elimination half-life is approximately 8 to 9 hours but earlier elimination rates are much more rapid, equivalent to a half-life of 1-2 hours; a consequence is the need for frequent (every 4 hours) dosing. Nimodipine is over 95% bound to plasma proteins. Nimodipine is eliminated almost exclusively in the form of metabolites and less than 1% is recovered in the urine as unchanged drug. Because of a high first-pass metabolism, the bioavailability of Nimodipine averages 13% after oral administration. The bioavailability is significantly increased in patients with hepatic cirrhosis, with Cmax approximately double that in normals which necessitates lowering the dose in this group of patients.