Effect of nimodipine, a dihydropyridine calcium channel antagonist on the pharmacokinetics of carbamazepine in rhesus monkeys. 2003

M C Gupta, and S K Garg, and B P Das, and V K Bhargava
Department of Pharmacology, Post Graduate Institute of Medical Education & Research, Chandigarh 160 012.

Calcium channel antagonists have been shown to have an anticonvulsant activity in a variety of seizure models and also to potentiate the anticonvulsant activity of other standard antiepileptic drugs like carbamazepine, phenytoin and valporoate. A pharmacokinetic interaction may be involved in such potentiation. This cross over single dose study was carried out to find out if there was a pharmacokinetic interaction between carbamazepine, a commonly used antiepileptic drug and nimodipine, a dihydropyridine calcium channel antagonist in rhesus moneys. Carbamazepine 46 mg/kg and nimodipine 9.6 mg/kg was administered through a nasogastric tube and blood samples were collected at 0.5, 1, 2, 3, 6, 9, 12, 24, 48, 72 and 96 hours after drug administration and were assayed for carbamazepine. Nimodipine caused a significant increase in peak plasma concentration (C(max)) of carbamazepine and a decrease in plasma absorption half life (t1/2 alpha). There was no significant change in other pharmacokinetic parameters between the two groups. The results of the study suggest that concurrent administration of carbamazepine and nimodipine may cause a significant rise in carbamazepine concentration as may contribute to a potentiation of anticonvulsant effect of carbamazepine and an increase in the incidence of adverse effects warranting that nimodipine should be prescribed cautiously in epileptic patients receiving carbamazepine and it might be very appropriate to do therapeutic drug monitoring of carbamazepine in such patients.

UI MeSH Term Description Entries
D008253 Macaca mulatta A species of the genus MACACA inhabiting India, China, and other parts of Asia. The species is used extensively in biomedical research and adapts very well to living with humans. Chinese Rhesus Macaques,Macaca mulatta lasiota,Monkey, Rhesus,Rhesus Monkey,Rhesus Macaque,Chinese Rhesus Macaque,Macaca mulatta lasiotas,Macaque, Rhesus,Rhesus Macaque, Chinese,Rhesus Macaques,Rhesus Macaques, Chinese,Rhesus Monkeys
D008297 Male Males
D009553 Nimodipine A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure. Admon,Bay e 9736,Brainal,Calnit,Kenesil,Modus,Nimodipin Hexal,Nimodipin-ISIS,Nimodipino Bayvit,Nimotop,Nymalize,Remontal,Bayvit, Nimodipino,Hexal, Nimodipin,Nimodipin ISIS,e 9736, Bay
D002121 Calcium Channel Blockers A class of drugs that act by selective inhibition of calcium influx through cellular membranes. Calcium Antagonists, Exogenous,Calcium Blockaders, Exogenous,Calcium Channel Antagonist,Calcium Channel Blocker,Calcium Channel Blocking Drug,Calcium Inhibitors, Exogenous,Channel Blockers, Calcium,Exogenous Calcium Blockader,Exogenous Calcium Inhibitor,Calcium Channel Antagonists,Calcium Channel Blocking Drugs,Exogenous Calcium Antagonists,Exogenous Calcium Blockaders,Exogenous Calcium Inhibitors,Antagonist, Calcium Channel,Antagonists, Calcium Channel,Antagonists, Exogenous Calcium,Blockader, Exogenous Calcium,Blocker, Calcium Channel,Blockers, Calcium Channel,Calcium Blockader, Exogenous,Calcium Inhibitor, Exogenous,Channel Antagonist, Calcium,Channel Blocker, Calcium,Inhibitor, Exogenous Calcium
D002220 Carbamazepine A dibenzazepine that acts as a sodium channel blocker. It is used as an anticonvulsant for the treatment of grand mal and psychomotor or focal SEIZURES. It may also be used in the management of BIPOLAR DISORDER, and has analgesic properties. Amizepine,Carbamazepine Acetate,Carbamazepine Anhydrous,Carbamazepine Dihydrate,Carbamazepine Hydrochloride,Carbamazepine L-Tartrate (4:1),Carbamazepine Phosphate,Carbamazepine Sulfate (2:1),Carbazepin,Epitol,Finlepsin,Neurotol,Tegretol
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D006207 Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Halflife,Half Life,Half-Lifes,Halflifes
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000927 Anticonvulsants Drugs used to prevent SEIZURES or reduce their severity. Anticonvulsant,Anticonvulsant Drug,Anticonvulsive Agent,Anticonvulsive Drug,Antiepileptic,Antiepileptic Agent,Antiepileptic Agents,Antiepileptic Drug,Anticonvulsant Drugs,Anticonvulsive Agents,Anticonvulsive Drugs,Antiepileptic Drugs,Antiepileptics,Agent, Anticonvulsive,Agent, Antiepileptic,Agents, Anticonvulsive,Agents, Antiepileptic,Drug, Anticonvulsant,Drug, Anticonvulsive,Drug, Antiepileptic,Drugs, Anticonvulsant,Drugs, Anticonvulsive,Drugs, Antiepileptic

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