Intravenous Carbamazepine: Comparison of Different Parenteral Formulations in a Mouse Model of Convulsive Status Epilepticus

Löscher, Wolfgang; Hönack, Dagmar

doi:10.1111/j.1528-1157.1997.tb01084.x

Cited by 30 publications

(9 citation statements)

References 23 publications

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“…Carbamazepine (CBZ) is an established treatment for focal epilepsy in adults, but no parenteral formulation is available [150]. In one small series, rectal CBZ syrup appeared to help prevent relapse in patients whose cluster of seizures in GCSE had been halted earlier [151].…”

Section: Non-sedating Drugs In the Treatment Of Rsementioning

confidence: 99%

Treatment of Refractory and Super-refractory Status Epilepticus

Rai

Drislane

2018

Neurotherapeutics

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Refractory and super-refractory status epilepticus (SE) are serious illnesses with a high risk of morbidity and even fatality. In the setting of refractory generalized convulsive SE (GCSE), there is ample justification to use continuous infusions of highly sedating medications-usually midazolam, pentobarbital, or propofol. Each of these medications has advantages and disadvantages, and the particulars of their use remain controversial. Continuous EEG monitoring is crucial in guiding the management of these critically ill patients: in diagnosis, in detecting relapse, and in adjusting medications. Forms of SE other than GCSE (and its continuation in a "subtle" or nonconvulsive form) should usually be treated far less aggressively, often with nonsedating anti-seizure drugs (ASDs). Management of "non-classic" NCSE in ICUs is very complicated and controversial, and some cases may require aggressive treatment. One of the largest problems in refractory SE (RSE) treatment is withdrawing coma-inducing drugs, as the prolonged ICU courses they prompt often lead to additional complications. In drug withdrawal after control of convulsive SE, nonsedating ASDs can assist; medical management is crucial; and some brief seizures may have to be tolerated. For the most refractory of cases, immunotherapy, ketamine, ketogenic diet, and focal surgery are among several newer or less standard treatments that can be considered. The morbidity and mortality of RSE is substantial, but many patients survive and even return to normal function, so RSE should be treated promptly and as aggressively as the individual patient and type of SE indicate.

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Section: Non-sedating Drugs In the Treatment Of Rsementioning

confidence: 99%

Treatment of Refractory and Super-refractory Status Epilepticus

Rai

Drislane

2018

Neurotherapeutics

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“…Carbamazepine (CBZ) is arguably the most widely used AED; it is clinically effective against partial and generalized convulsive seizures, but its aqueous insolubility and short half-life are major drawbacks for designing chronic experiments that require prolonged administration (Loscher & Honack, 1997). Therefore, CBZ is an appropriate ''test AED'' for a ''proof-of-principle'' study on chronic AED administration in animal models of epilepsy.…”

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confidence: 99%

A once‐per‐day, drug‐in‐food protocol for prolonged administration of antiepileptic drugs in animal models

et al. 2011

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SUMMARYPurpose: Convenient and effective methods for administering potential antiepileptic drugs (AEDs) chronically should facilitate many experiments in animal models of chronic epilepsy with spontaneous recurrent seizures. This proof-of-principle study aimed to optimize a once-per-day, drug-in-food protocol by testing the effect of carbamazepine (CBZ) on the frequency of convulsive seizures in rats with kainate-induced epilepsy. Methods: Adult male rats were given repeated low-dose kainate injections until convulsive status epilepticus persisted for >3 h. After the rats developed spontaneous recurrent seizures, food pellets with CBZ (30, 100, or 300 mg/kg/day) were provided once per day in three 2-week trials (n = 7-9 rats) involving 5 days of CBZ or control treatment, separated by two recovery days within a trial. The total amount of food provided and consumed per day corresponded to a normal caloric diet (60 g/kg/ day). Key Findings: When provided once per day, all animals ate the CBZ-containing food irregularly but continuously throughout the 24-h day. With this daily feeding protocol, CBZ significantly reduced the frequency of spontaneous convulsive seizures in a dose-dependent manner. It is important to note that the effect of CBZ was consistent across the 5 days and throughout each day of the trials. With food administered at 9:00 a.m., and blood assayed at 5:00 p.m., higher food levels of CBZ resulted in higher plasma concentrations of CBZ. Significance: This AED-in-food protocol is simple, efficient, inexpensive, reliable, and noninvasive; it allows easier long-term drug administration and is less stressful and more humane than other methods of AED administration.

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“…Carbamazepine (CBZ) is available as tablets and suspension for acute treatment of seizures. However certain formulations of CBZ, for intravenous administration, CBZ dissolved in glycofurol [7] and CBZ solubilized with 2-hydroxypropylb-cyclodextrin [8] are reported. Two lipid formulations of CBZ are reported, one is a parenteral formulation of CBZ developed using SolEmuls technology [9] in which the CBZ is solubilized in the interfacial layer of a lipid emulsion (lipofundin) by high pressure homogenization and the other is slow release lipospheres of CBZ prepared by melt dispersion technique [10].…”

Section: Journal Of Molecular Pharmaceutics and Organic Process Researchmentioning

confidence: 99%

Brain Targeting Potential of Intravenous Carbamazepine SNEDDS

Kumar¹,

Rambhau²

2017

J Mol Pharm Org Process Res

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Purpose: The objective of this study was to evaluate the ability of nano-droplets of Self Nano Emulsifying Drug Delivery System to diffuse into the brain tissue. Methods:The preconcentrate was prepared by dissolving oils, surfactants and cosolvents in 1:1 mixture of methanol and chloroform and flash evaporated at 50°C and was stored at room temperature until their use in subsequent studies. CSEDD with surfactant polysorbate-80 were radiolabelled with radioactive C18 triglyceride. The nanodroplets formed by CSEDD in 5% dextrose were subjected to evaluation in blood and brain. Results:The intravenous pharmacokinetics of carbamazepine in rats of CSEDD formulation generated high initial serum levels (5.25 mcg/ml) at 0.25 h when compared to C-Sol (3.91 mcg/ml) at 0.5 h. It was found that oil to surfactant ratio had an impact on the physical characteristics of the nano-emulsion formed. The brain levels of CBZ from optimized CSEDD were significantly high at all-time points when compared to plain solution. The initial levels of CBZ from CSEDD was 8.023 mcg/ml thereafter the levels were consistently high till 8 h and the initial levels of CBZ from plain solution was 3.62 mcg/ml followed by a gradual decline till 4 h evidently showing that the clearance of CBZ from CSEDD was reduced. The brain targeting index of CSEDD and solution were 3 and 2 respectively. The brain enhancement factor value was found to be 22.29 at 15 min revealing a very rapid penetration of CBZ into brain. Conclusions:This study proposes intravenous CSEDD as a new brain delivery system and highlights two requirements to design adequate delivery systems for long circulating properties of the carrier and appropriate surface characteristics to allow interactions with BBB endothelial cells.

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Intravenous Carbamazepine: Comparison of Different Parenteral Formulations in a Mouse Model of Convulsive Status Epilepticus

Cited by 30 publications

References 23 publications

Treatment of Refractory and Super-refractory Status Epilepticus

Treatment of Refractory and Super-refractory Status Epilepticus

A once‐per‐day, drug‐in‐food protocol for prolonged administration of antiepileptic drugs in animal models

Brain Targeting Potential of Intravenous Carbamazepine SNEDDS

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