Pharmacokinetics and Metabolism of Calcium-Blocking Agents Nifedipine, Nitrendipine, and Nimodipine

Rämsch, K.‐D.; Graefe, Karl Heinz; Scherling, D.; Sommer, J.; Ziegler, Ralph

doi:10.1159/000167224

Cited by 72 publications

(24 citation statements)

References 13 publications

(15 reference statements)

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“…For example, our results in orally-dosed rabbits suggested that even four daily doses, 6 h apart, would not likely be adequate to maintain desired serum concentrations. The low concentrations observed using oral dosing are not surprising considering the important first-pass effect of hepatic metabolism on nimodipine following oral administration (Ramsch et al, 1985(Ramsch et al, , 1986Vinge et al, 1986;Langley and Sorkin, 1989). Low plasma concentrations of nimodipine following oral administration in healthy human subjects and SAH patients have been well-documented in the literature (Gengo et al, 1987;Haws et al, 1983;Ramsch et al, 1986;Vinge et al, 1986).…”

Section: Discussionmentioning

confidence: 99%

“…The frequency of this dosing regimen reflects the low bioavailability of orally-administered nimodipine. Pharmacokinetic studies show that the bioavailability of orally-administered nimodipine is between 4 and 13% in healthy subjects (Ramsch et al, 1985(Ramsch et al, , 1986; it is also low in SAH patients, ranging from 2 to 28% (Vinge et al, 1986). Low plasma concentrations following orally-administered nimodipine are attributed to the high first-pass metabolism of nimodipine in the liver (Ramsch et al, 1985).…”

Section: Introductionmentioning

confidence: 99%

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Subcutaneous administration of nimodipine improves bioavailability in rabbits

Laslo¹,

Eastwood²,

Urquhart³

et al. 2004

Journal of Neuroscience Methods

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Subcutaneous administration of nimodipine improves bioavailability in rabbits

Laslo¹,

Eastwood²,

Urquhart³

et al. 2004

Journal of Neuroscience Methods

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“…The pharmacokinetics of nimodipine after oral administration was assessed in patients to which the drug was administered in capsules (34)(35)(36), tablets (37,38), or as an oral solution (38). Pharmacokinetics of nimodipine were also studied after intravenous (IV) administration (38,39).…”

Section: Pharmacokineticsmentioning

confidence: 99%

Nimodipine and Its Use in Cerebrovascular Disease: Evidence from Recent Preclinical and Controlled Clinical Studies

Tomassoni

Lanari

Silvestrelli

et al. 2008

Clinical and Experimental Hypertension

119

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Nimodipine is a 1,4-dihydropyridine-derivative Ca(2+)-channel blocker developed approximately 30 years ago. It is highly lipophilic, crosses the blood-brain barrier, and reaches brain and cerebrospinal fluid. Early treatment with nimodipine reduces the severity of neurological deficits resulting from vasospasm in subarachnoid haemorrhage (SAH) patients. In SAH, nimodipine reduced spasm-related deficits of all severities, but no spasm-unrelated deficits. This paper has reviewed preclinical studies on the influence of nimodipine in various animal models of cerebral ischemia, with particular attention toward investigations published in the last 10 years. These studies further support the main indication of nimodipine, by clarifying some mechanisms of the anti-ischemic activity of the compound. Papers reporting a possible role of nimodipine in epileptogenesis were also examined. Clinical studies on nimodipine were grouped into subarachnoid hemorrhage, acute ischemic stroke, cerebral ischemia without stroke, dementia disorders, and migraine. Clinical investigations have shown that the drug improves neurological outcome by reducing the incidence and severity of ischemic deficits in patients with SAH from ruptured intracranial berry aneurysms regardless of their post-ictus neurological condition. No relevant effects of treatment with nimodipine were reported for acute ischemic stroke, cerebral ischemia without stroke, and migraine, except than for cluster headache. The less pronounced cardiovascular effects of nimodipine compared to other dihydropyridine-type Ca(2+)-channel blockers probably accounts for its use out of label for treating patients affected by chronic cerebral ischemia and vascular cognitive impairment. However, the blood pressure-lowering effects of nimodipine should not be minimized, as clinical studies have documented lowering blood pressure in small groups of patients, including cases of withdrawn due to pronounced hypotension induced by nimodipine administration. In the area of vascular cognitive impairment, short-term benefits of nimodipine do not justify its use as a long-term anti-dementia drug, and benefits obtained in elderly patients affected by subcortical vascular dementia require to be confirmed by other groups and in larger scale trials. In conclusion, nimodipine is a safe drug with an important place in pharmacotherapy and with the main documentation for reduction in the severity of neurological deficits resulting from vasospasm in SAH patients.

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“…The standard method of dosing calls for a 60-mg oral dose to be given every 4 hours for 21 days (6). The frequency of this dosing regimen reflects the low bioavailability of orally administered nimodipine, attributed to its high first-pass metabolism in the liver (29). Intravenous nimodipine is an alternative to oral administration that provides greater bioavailability and more stable plasma concentrations than oral dosing (18,35,38).…”

Section: Introductionmentioning

confidence: 99%