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Pharmacology
Description
Nimotop® (nimodipine) belongs to the class of pharmacological agents known as calcium channel blockers. Nimodipine is isopropyl 2 - methoxyethyl 1, 4 - dihydro - 2, 6 - dimethyl - 4 - (m - nitrophenyl) - 3, 5 - pyridinedicarboxylate. It has a molecular weight of 418.5 and a molecular formula of C21H26N2O7. The structural formula is:1
Nimodipine is a yellow crystalline substance, practically insoluble in water.
NIMOTOP® capsules are formulated as soft gelatin capsules for oral administration. Each liquid filled capsule contains 30 mg of nimodipine in a vehicle of glycerin, peppermint oil, purified water and polyethylene glycol 400. The soft gelatin capsule shell contains gelatin, glycerin, purified water and titanium dioxide.1
Clinical Pharmacology
Mechanism of Action: 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. In animal experiments, 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.1
The precise mechanism of action of nimodipine in humans is unknown. Although the clinical studies described below demonstrate 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. However, whether or not the arteriographic methodology utilized was adequate to detect a clinically meaningful effect, if any, on vasospasm is unknown.1
Pharmacokinetics and Metabolism: In man, 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. There were no signs of accumulation when nimodipine was given three times a day for seven days. Nimodipine is over 95% bound to plasma proteins. The binding was concentration independent over the range of 10 ng/mL to 10 µg/mL. Nimodipine is eliminated almost exclusively in the form of metabolites and less than 1% is recovered in the urine as unchanged drug. Numerous metabolites, all of which are either inactive or considerably less active than the parent compound, have been identified. 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 (click here to read about Dosage and Administration). In a study of 24 health male volunteers, administration of nimodipine capsules following a standard breakfast resulted in a 68% lower peak plasma concentration and 38% lower bioavailability relative to dosing under fasted conditions.1
In a single parallel-group study involving 24 elderly subjects (aged 59-79) and 24 younger subjects (aged 22-40), the observed AUC and Cmax of nimodipine was approximately 2-fold higher in the elderly population compared to the younger study subjects following oral administration (given as a single dose of 30 mg and dosed to steady-state with 30 mg t.i.d. for 6 days). The clinical response to these age-related pharmacokinetic differences, however, was not considered significant.1
Sources:
- Nimotop® (nimodipine) Capsules Prescribing Information
December 2005
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DO NOT ADMINISTER NIMOTOP INTRAVENOUSLY OR BY OTHER PARENTERAL ROUTES. DEATHS AND SERIOUS, LIFE-THREATENING ADVERSE EVENTS HAVE OCCURRED WHEN THE CONTENTS OF NIMOTOP CAPSULES HAVE BEEN INJECTED PARENTERALLY
(See
WARNINGS and DOSAGE AND ADMINISTRATION.) |
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- In patients with SAH, Nimotop® controls damage with a low side effect profile.
- Decreased blood pressure is the most common side effect, occurring in 4.4% of patients. Blood pressure should be monitored during therapy.1
- Other side effects occurring at a low frequency of ≥1.0% include headache, nausea, and bradycardia.1
- No clinically significant effects on hematologic factors, renal or hepatic function, or carbohydrate metabolism have been causally associated with oral nimodipine.1
- Nimotop® does not appear to affect anesthetic management.2
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Sources:
- Nimotop® (nimodipine) Capsules Prescribing
Information December 2005
- Stullken EH, Johnston WE, Prough DS. Implications of nimodipine prophylaxis of cerebral vasospasm on anesthetic management during intracranial aneurysm clipping. J. Neurosurg. 1985; 62:200-205.
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© Bayer HealthCare Pharmaceuticals.
Bayer HealthCare Pharmaceuticals
6 West Belt
Wayne, NJ 07470
The information provided on Bayer products is only intended for the United States audience. Regulatory requirements, regulations, laws, and distribution of information about drug products may vary from country to country. Product names and indications (product uses) also may be different in different countries. The prescribing information provided here is based on United States labeling and may not be appropriate outside of the US.
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