An automated method for the determination of a new potential antiepileptic agent (CGP 33101) in human plasma using high performance liquid chromatography

Brunner, Linda A.; Powell, Mark L.

doi:10.1002/bmc.1130060606

Cited by 24 publications

(7 citation statements)

References 3 publications

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“…Plasma rufinamide concentrations were determined using a validated high‐performance liquid chromatography (HPLC) assay with ultraviolet (UV) or tandem mass spectrometry (MS) detection (Brunner & Powell, 1992; Brunner et al, 1994). Routes of elimination were investigated using 14 C‐labelled rufinamide.…”

Section: Methodsmentioning

confidence: 99%

Rufinamide: Clinical pharmacokinetics and concentration–response relationships in patients with epilepsy

et al. 2008

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SUMMARYRufinamide is a new, orally active antiepileptic drug (AED), which has been found to be effective in the treatment of partial seizures and drop attacks associated with the Lennox-Gastaut syndrome. When taken with food, rufinamide is relatively well absorbed in the lower dose range, with approximately dose-proportional plasma concentrations up to 1,600 mg/day, but less than dose-proportional plasma concentrations at higher doses due to reduced oral bioavailability. Rufinamide is not extensively bound to plasma proteins. During repeated dosing, steady state is reached within 2 days, consistent with its elimination half-life of 6-10 h. The apparent volume of distribution (V d /F) and apparent oral clearance (CL/F) are related to body size, the best predictor being body surface area. Rufinamide is not a substrate of cytochrome P450 (CYP450) enzymes and is extensively metabolized via hydrolysis by carboxylesterases to a pharmacologically inactive carboxylic acid derivative, which is excreted in the urine. Rufinamide pharmacokinetics are not affected by impaired renal function. Potential differences in rufinamide pharmacokinetics between children and adults have not been investigated systematically in formal studies. Although population pharmacokinetic modeling suggests that in the absence of interacting comedication rufinamide CL/F may be higher in children than in adults, a meaningful comparison of data across age groups is complicated by age-related differences in doses and in proportion of patients receiving drugs known to increase or to decrease rufinamide CL/F. A study investigating the effect of rufinamide on the pharmacokinetics of the CYP3A4 substrate triazolam and an oral contraceptive interaction study showed that rufinamide has some enzyme-inducing potential in man. Findings from population pharmacokinetic modeling indicate that rufinamide does not modify the CL/F of topiramate or valproic acid, but may slightly increase the CL/F of carbamazepine and lamotrigine and slightly decrease the CL/F of phenobarbital and phenytoin (all predicted changes were <20%). These changes in the pharmacokinetics of associated AEDs are unlikely to make it necessary to change the dosages of these AEDs given concomitantly with rufinamide, with the exception that consideration should be given to reducing the dose of phenytoin. Based on population pharmacokinetic modeling, lamotrigine, topiramate, or benzodiazepines do not affect the pharmacokinetics of rufinamide, but valproic acid may increase plasma rufinamide concentrations, especially in children in whom plasma rufinamide concentrations could be increased substantially. Conversely, comedication with carbamazepine, vigabatrin, phenytoin, phenobarbital, and primidone was associated with a slight-to-moderate decrease in plasma rufinamide concentrations, ranging from a minimum of −13.7% in female children comedicated with vigabatrin to a maximum of −46.3% in female adults comedicated with phenytoin, phenobarbital, or primidone. In population modeling using data from plac...

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Section: Methodsmentioning

confidence: 99%

Rufinamide: Clinical pharmacokinetics and concentration–response relationships in patients with epilepsy

et al. 2008

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“…RFN has received Orphan Drug status in both the European Union and the United States for adjunctive therapy in patients with partial seizures and drop attacks associated with the Lennox-Gastaut syndrome [1]. Two HPLC-UV methods coupled with automated procedures utilizing laboratory robotics have been reported for the determination of RFN in body fluids during early pharmaceutical development [2,3]: after plasma dilution with water RFN was automatically extracted on reversed-phase extraction columns and injected into the HPLC system. Neither of these methods has been validated in plasma of patients with epilepsy.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous HPLC–UV analysis of rufinamide, zonisamide, lamotrigine, oxcarbazepine monohydroxy derivative and felbamate in deproteinized plasma of patients with epilepsy

Contin

Mohamed

Candela

et al. 2010

Journal of Chromatography B

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“…Analytical methods for RFM from pharmaceutical dosage form should be developed and validated. To date, all analytical methods described in literature for the determination of RFM in biological fluids involve liquid chromatography [3][4][5][6][7] and liquid chromatography-mass spectrometry methods [8][9] .…”

Section: Research Articlementioning

confidence: 99%

Novel Spectrophotometric Methods for the Quantitative Analysis of Rufinamide in Pharmaceutical Dosage Forms

Annapurna¹,

Krishna²,

PADMAKAR³

et al. 2012

Chem Sci Trans

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Two simple, rapid and sensitive spectrophotometric methods were developed for the determination of rufinamide in pharmaceutical formulations in phosphate buffer pH 8.0 and borate buffer pH 9.0. Beer's law was obeyed in a concentration range of 0.5-30 μg/mL in phosphate buffer pH 8.0 and borate buffer pH 9.0 respectively with correlation coefficient of r 2 =0.999 in both the methods. The linear regression equations are found to be y=0.0867x + 0.0241 and y = 0.0898x + 0.0345 in phosphate and borate buffer respectively. The % RSD for intra-day and inter-day precision studies were found to be 0.32 and 0.67 in phosphate buffer pH 8.0 and 0.28 and 0.59 in borate buffer pH 9.0 respectively which is less than 2.0 indicating that the methods are precise. The % RSD in accuracy studies was also found to be less than 2.0. The proposed methods are suitable for the determination of rufinamide in pharmaceutical formulations. No interferences were observed from the excipients in the formulations. The methods were validated according to ICH guidelines.

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An automated method for the determination of a new potential antiepileptic agent (CGP 33101) in human plasma using high performance liquid chromatography

Cited by 24 publications

References 3 publications

Rufinamide: Clinical pharmacokinetics and concentration–response relationships in patients with epilepsy

Rufinamide: Clinical pharmacokinetics and concentration–response relationships in patients with epilepsy

Simultaneous HPLC–UV analysis of rufinamide, zonisamide, lamotrigine, oxcarbazepine monohydroxy derivative and felbamate in deproteinized plasma of patients with epilepsy

Novel Spectrophotometric Methods for the Quantitative Analysis of Rufinamide in Pharmaceutical Dosage Forms

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