Nimodipine

Nimodipine is a calcium channel blocker. The muscle cells in the walls of blood vessels need calcium ions to contract. These ions enter the cells slowly when the cells are activated. Nimodipine blocks calcium from getting into these cells, so the blood vessel muscle relaxes and contracts less. The drug has a stronger effect on the arteries in the brain than on arteries elsewhere in the body. This may be because it is highly lipophilic, which lets it cross the blood-brain barrier. In patients with subarachnoid hemorrhage (SAH) who were taking nimodipine, levels as high as 12.5 ng/mL have been found in the cerebrospinal fluid. Exactly how nimodipine works in SAH in humans is not known. Clinical studies show that it improves the severity of neurological deficits caused by cerebral vasospasm after SAH. However, there is no arteriographic evidence that the drug either prevents or relieves the spasm in these arteries.

Nimodipine is absorbed quickly after it is taken by mouth, and peak levels are usually reached within one hour. The final elimination half-life is about 8 to 9 hours, but in the early stage the drug clears much faster, with a half-life of 1 to 2 hours. Because of this, the medicine has to be given frequently, every 4 hours. More than 95% of nimodipine binds to plasma proteins. Almost all of it is eliminated as metabolites, and less than 1% is found in the urine as unchanged drug. Much of the dose is broken down in the liver before it reaches the general circulation (high first-pass metabolism), so the bioavailability of nimodipine after oral use averages 13%. In patients with hepatic cirrhosis, bioavailability is much higher. Their Cmax is about double that of healthy people, so the dose needs to be lowered in this group.