Pharmacokinetic Modeling of Intra-arterial Nimodipine Therapy for Subarachnoid Hemorrhage-Related Cerebral Vasospasm.
OBJECTIVE
Intra-arterial (IA) administration of nimodipine has been shown to be an effective treatment for subarachnoid hemorrhage-related cerebral vasospasm. The concentrations achieved in cerebral arteries during this procedure, though, are unknown. Therefore, there are no clinical studies investigating dose-dependent effects of nimodipine. We aimed at providing a pharmacokinetic model for IA nimodipine therapy for this purpose.


METHODS
A two-compartment pharmacokinetic model for intravenous nimodipine therapy was modified and used to assess cerebral arterial nimodipine concentration during IA nimodipine infusion into the internal carotid artery (ICA).


RESULTS
According to our simulations, continuous IA nimodipine infusion at 2 mg/h and 1 mg/h resulted in steady-state cerebral arterial concentrations of about 200 ng/ml and 100 ng/ml assuming an ICA blood flow of 200 ml/min and a clearance of 70 l/h. About 85 % of the maximal concentration is achieved within the first minute of IA infusion independent on the infusion dose. Within the range of physiological and pharmacokinetic data available in the literature, ICA blood flow has more impact on cerebral arterial concentration than nimodipine clearance.


CONCLUSIONS
The presented pharmacokinetic model is suitable for estimations of cerebral arterial nimodipine concentration during IA infusion. It may, for instance, assist in dose-dependent analyses of angiographic results.
Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany.
F
F
Seker
Experimental Radiation Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
J
J
Hesser
Clinic for Diagnostic and Interventional Neuroradiology, University Hospital of the RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany.
M A
MA
Brockmann
Department of Neuroradiology, University Medical Center Mannheim, Mannheim, Germany.
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E
Neumaier-Probst
Department of Neuroradiology, University Medical Center Mannheim, Mannheim, Germany.
C
C
Groden
Research Division Cardiovascular Physiology, Centre for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
R
R
Schubert
Clinic for Diagnostic and Interventional Neuroradiology, University Hospital of the RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany. caro.brockmann@gmx.de.
C
C
Brockmann
D003198:Computer Simulation; D006801:Humans; D007269:Injections, Intra-Arterial; D008657:Metabolic Clearance Rate; D008955:Models, Cardiovascular; D009553:Nimodipine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D020301:Vasospasm, Intracranial / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*
D014665:Vasodilator Agents; D009553:Nimodipine
Aneurysmal subarachnoid hemorrhage; Calcium channel antagonist; Cerebral vasospasm; Simulation