Nimodipine levels in gerbil brain following parenteral drug administration

D. S. Heffez, Thaddeus Nowak, J. V. Passonneau

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Nimodipine binding to the particulate fraction of gerbil brain homogenate was characterized using tritiated (3H)-nimodipine as the radioactive ligand. Binding was monophasic and saturable, with the apparent affinity constant (K(D)) = 0.4 nM and the maximum number of binding sites (B(max)) = 12 nmol/kg wet wt. A competitive binding assay was validated for the measurement of nimodipine using gerbil brain as the source of receptors for the drug. Binding characteristics were sufficiently similar in specimens from different animals to allow the use of homogenates from individual animals as the source of both membrane-binding sites and competing ligand. Nimodipine could be detected in the brains of animals sacrificed soon after drug injection, and reached a peak level within 15 minutes. Brain drug level at a given time was a linear function of dose administered. One hour after a 1-mg/kg dose, the level of drug measured in brain was approximately 100 nmol/kg wet wt, more that 200 times the K(D). Sufficient drug to mediate a maximal pharmacological effect accumulated in brain even after a dose of only 0.25 mg/kg. Thus, in this species, effective tissue nimodipine levels may be achieved at doses which minimize the risk of systemic hypotension.

Original languageEnglish (US)
Pages (from-to)589-592
Number of pages4
JournalJournal of Neurosurgery
Volume63
Issue number4
DOIs
StatePublished - Jan 1 1985
Externally publishedYes

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Nimodipine
Gerbillinae
Brain
Pharmaceutical Preparations
Binding Sites
Ligands
Drug Receptors
Competitive Binding
Hypotension
Pharmacology
Injections
Membranes

All Science Journal Classification (ASJC) codes

  • Surgery
  • Clinical Neurology

Cite this

Nimodipine levels in gerbil brain following parenteral drug administration. / Heffez, D. S.; Nowak, Thaddeus; Passonneau, J. V.

In: Journal of Neurosurgery, Vol. 63, No. 4, 01.01.1985, p. 589-592.

Research output: Contribution to journalArticle

Heffez, D. S. ; Nowak, Thaddeus ; Passonneau, J. V. / Nimodipine levels in gerbil brain following parenteral drug administration. In: Journal of Neurosurgery. 1985 ; Vol. 63, No. 4. pp. 589-592.
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