Relationships between pharmacokinetic parameters of carbamazepine and therapeutic response in patients with bipolar disease

Chbili, Chahra; Bannour, Souhail; Khlifi, Saida; Ali, B. Ben Hadj; Saguem, Saâd

doi:10.1684/abc.2014.0975

Cited by 5 publications

(4 citation statements)

References 17 publications

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“…In a previous study, a similar result was found in a group of patients with bipolar disorder who were treated with CBZ [ 17 ]. As evaluated by the Brief Psychiatric Rating Scale (BPRS) score, the optimal therapeutic efficacy was found when the plasma concentrations of CBZ and CBZ-E were simultaneously set at 7 μg/ml ( r = 0.28, p = 0.19) and 1.4 μg/ml ( r = 0.78, p = 0.0001), respectively [ 17 ]. In this case, the values obtained in the previous study are more meaningful than those obtained in our study.…”

Section: Discussionsupporting

confidence: 81%

“…The plasma samples were analyzed with high-performance liquid chromatography in the Metabolic Biophysics, Professional Toxicology, and Applied Environmental Laboratory, Department of Biophysics, Medicine Faculty of Sousse, Sousse, Tunisia. The determination of the plasma levels of CBZ and CBZ-E in human plasma was conducted using previously described high-performance liquid chromatography (HPLC)-based assays [ 17 ].…”

Section: Methodsmentioning

confidence: 99%

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The relationship between pharmacokinetic parameters of carbamazepine and therapeutic response in epileptic patients

Chbili¹,

Hassine²,

Laouani³

et al. 2017

aoms

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IntroductionThe prescribed dose and carbamazepine plasma concentration to achieve the optimal therapeutic efficacy are highly variable from one patient to the other. Our study aimed to determine whether biological parameters may be used as plasma markers that can individually adjust the carbamazepine dose necessary to optimize therapeutic efficacy.Material and methodsNinety-four epileptic patients under carbamazepine monotherapy and who have never used combination therapy were recruited from the consecutive admissions at the Department of Neurology “CHU Sahloul” of Sousse Central Hospital in Tunisia from February 2010 to April 2011. The patients were monitored for epilepsy for three years on average. Carbamazepine and 10,11-epoxide-carbamazepine concentrations were analyzed through high-performance liquid chromatography. Simultaneously, therapeutic efficacy was assessed through the annual number of seizures in each patient.ResultsOur results showed the absence of any significant correlations between specific dose (mg/kg/day), carbamazepine plasma concentrations and therapeutic efficacy (r = 0.0025, p = 0.30; r = 0.1584, p = 0.38 respectively), whereas both plasma 10,11-epoxide-carbamazepine concentration and 10,11-epoxide-carbamazepine to plasma carbamazepine ratio were closely correlated with therapeutic efficacy (r = 0.34, p = 0.03; r = 0.45, p = 0.008 respectively). The optimum therapeutic response was observed among patients who simultaneously had a plasma concentration of 0.8 μg/ml of metabolite and 5.5 μg/ml of carbamazepine.ConclusionsThe results suggest that plasma levels of both carbamazepine and of 10,11-epoxide-carbamazepine must be set to achieve an optimum therapeutic response.

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Section: Discussionsupporting

confidence: 81%

Section: Methodsmentioning

confidence: 99%

The relationship between pharmacokinetic parameters of carbamazepine and therapeutic response in epileptic patients

Chbili¹,

Hassine²,

Laouani³

et al. 2017

aoms

Self Cite

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“…The cytotoxic effect of CBZ was investigated using a wide range of concentrations from 1-1000 µM which cover all therapeutic, supra-therapeutic and toxic levels. The therapeutic level of CBZ was reported to be up to 12 mg/L (around 50µM), while the concentration of CBZ was reported to around 170 µM in cases of significant CBZ overdoses [32,33,34]. Higher concentrations were used to allow testing the chronic effect of the drug within the limited time frame of the experiment.…”

Section: Discussionmentioning

confidence: 99%

Carbamazepine induces oxidative stress on rats’ microvascular endothelial cells of the blood-brain barrier

Elmorsy¹

2020

Ann Clin Anal Med

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Aim: Carbamazepine (CBZ) is a commonly used anticonvulsant. Its effect on the blood-brain barrier(BBB) is poorly understood. Hence the current study had investigated the effect of CBZ on the isolated cultured microvascular epithelial cells of albino rats. Oxidative stress was investigated as the underlying mechanism of its cytotoxicity. Material and Method: Albino rats' microvascular endothelial cells (rMVECs) were isolated. CBZ induced cytotoxicity was evaluated by Alamar blue (AB) assay using concentrations range 1-1000µM. Oxidative stress markers as lipid peroxidation (TBARS), Catalase, superoxide dismutase(SOD), reduced glutathione(GSH), reactive oxygen species (ROS) were evaluated 24 hours after exposure to CBZ estimated IC50 and 50 µM. Also, the protective effect of anti-oxidation reduced GSH was studied. Results: AB assay showed that CBZ decreased the viability of the cells in relation to their concentrations and exposure durations. CBZ's 24 hours estimated IC50s was about 130µM. CBZ increased TBARS in the both 130 and 50 µM concentrations (p = 0.0009). CBZ significantly decreased SOD, catalase, and GSH levels in its estimated IC50s, while in the lower concentration (50 µM) only CBZ showed a significant effect on reduced GSH(p=0.003). Also, CBZ increased significantly (p=0.0018) ROS with both tested concentrations. Addition of reduced GSH significantly decreased the cytotoxic effect of CBZ in its estimated IC50s (p<0.0001) and in the concentration of 50 µM (p=0.0005). Discussion: CBZ can be cytotoxic to the BBB cells with disruption of its integrity which may expose the nervous system to various harmful circulating molecules. Also, co-administration of antioxidants with CBZ may have a protective role.

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“…An analysis of plasma samples were performed in the Laboratory of Metabolic Biophysics, Professional Toxicology and Applied Environnemental, Department of Biophysics, Medicine Faculty of Sousse, Sousse, Tunisia. Dosage of CBZ and CBZ-E was conducted using previously described high performance liquid chromatography [ 17 ].…”

Section: Methodsmentioning

confidence: 99%

Glutathione S-transferase M1 and T1 polymorphisms and the risk of mild hepatotoxicity induced by carbamazepine in a tunisian population study

et al. 2018

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BackgroundThe aim of this study was to evaluate whether the glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) null alleles may contribute to carbamazepine-induced hepatotoxicity.MethodsA cross-sectional prospective study was conducted to identify the frequency distribution of GSTM1 and GSTT1 alleles in 129 Tunisian epileptic patients treated with carbamazepine. Null alleles were determined using a Polymerase Chain Reaction. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured by standard methods.ResultsOur results showed that the frequencies of GSTM1 (−) null allele and GSTT1 null (−) allele were 74.4 and 17.8% respectively. The ALT and AST levels were elevated in 46 (35.7%) and 33 (25.6%) cases. The mean values of ALT and AST were approximately 1.32 and 3.61 times higher than the upper limit of normal levels, respectively. The values of ALT and AST were significantly higher in GSTM1 (−) allele than in GSTM1 (+) (p = 10−3.and 0.004, respectively).The level of ALT was significantly higher in combination of GSTM1 (−)/T1(−) than in combined GSTM1(−)/T1(+) and combined GSTM1(+)/T1(+) (p = 0.2 and 0.03, respectively), and that of AST was significantly higher in combination of GSTM1(−)/T1(−) and in combination of GSTM1(+)/T1(−) than in combination of GSTM1(+)/T1(+) (p = 10−3 and 10−3, respectively).ConclusionsOur findings suggest that the GSTM1 (−) allele may be considered as a key factor for the development of carbamazepine-induced hepatotoxicity. Results related to GSTT (−) allele and elevation in AST levels should be considered with caution as AST may be elevated in other pathophysiological conditions.

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Relationships between pharmacokinetic parameters of carbamazepine and therapeutic response in patients with bipolar disease

Cited by 5 publications

References 17 publications

The relationship between pharmacokinetic parameters of carbamazepine and therapeutic response in epileptic patients

The relationship between pharmacokinetic parameters of carbamazepine and therapeutic response in epileptic patients

Carbamazepine induces oxidative stress on rats’ microvascular endothelial cells of the blood-brain barrier

Glutathione S-transferase M1 and T1 polymorphisms and the risk of mild hepatotoxicity induced by carbamazepine in a tunisian population study

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