The effect of combination therapy on the plasma concentrations of traditional antiepileptics

Sırmagül, Başar; Atlı, Özlem; Ilgın, Sinem

doi:10.1177/0960327112446516

Cited by 9 publications

(8 citation statements)

References 36 publications

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“…In the studies reported earlier, about 7-33 % of the epileptic patients received more than a single antiepileptic drug simultaneously. 4,7,10 In our study, the average plasma concentration of phenytoin, carbamazepine, phenobarbitone and sodium valproate were 8.68±79, 6.03±3.24, 6.00±0 and 185.12±21 mcg/ml respectively in patients receiving monotherapy, 44 % of samples found to be in the therapeutic range. The plasma concentration values were within the therapeutic range for carbamazepine, below the therapeutic range for phenytoin and phenobarbitone and well above the range for sodium valproate.…”

Section: Discussionsupporting

confidence: 48%

“…3 The plasma concentration of AEDs can be influenced by many factors like age, gender, duration of epileptic disorder, drug interactions with concomitant drugs, compliance, co-morbid conditions of the patient as well as the genetic make-up of the individual. [4][5][6] Phenytoin, phenobarbitone and carbamazepine are inducers of cytochrome enzymes and sodium valproate is an inhibitor of these enzymes. 7 When a patient receives a combination of these drugs, the interactions can reduce the effect of drug therapy and/or can cause adverse effects.…”

Section: Introductionmentioning

confidence: 99%

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Factors Influencing Plasma Concentrations of Phenytoin, Phenobarbitone, Carbamazepine and Sodium Valproate in Epileptic Patients Attending a Tertiary Care Hospital

Jagennath

Raj

Mathaiyan

2019

IJPI

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Objective: The traditional anti-epileptic drugs like phenytoin, sodium valproate and carbamazepine continue to be used widely in the low to middle income countries due to their time tested efficacy and low costs. The factors which affect the AED concentrations in non-toxicity indications has not been reported so far. Hence, we studied the factors that could influence the plasma concentrations of these AEDs. Methods: This is a retrospective record based study and a short term prosepective study. Requisition forms of epileptic patients referred for TDM 2012-2014 were compared with the AED concentrations reported. Epileptic patients who were referred during May-June 2015 for TDM were evaluated for their seizure history and anthropometic measurements for calculation of extracellular volume (V ECW ) and compared with the AED concentrations. Results: Out of the 170 requisitions for TDM, 68.2% were monotherapy and 31.8% received two or more antiepileptic drugs. In 44% of patients, the plasma concentrations of the AED correlated with clinical response. In our study the plasma level of carbamazepine was found to be reduced by phenytoin, sodium valproate concentration was reduced by carbamazepine and phenytoin levels were reduced by sodium valproate. In male, phenytoin levels were significantly lower than in female, Phenytoin decreased carbamazepine levels significantly in female. Carbamazepine significantly decreased sodium valproate concentrations in females. Carbamazepine dose adjusted for weight and V ECW was found to show a trend of correlation to the blood levels, Conclusion: TDM for AEDs is an indispensable investigation that guides the clinicians to tailor dose of drugs in individual patients. Factors such as age, gender, concomitant drugs in general and V ECW in patients on carbamazepine needs to be considered while interpreting AED plasma concentrations for monitoring therapy.

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Section: Discussionsupporting

confidence: 48%

Section: Introductionmentioning

confidence: 99%

Factors Influencing Plasma Concentrations of Phenytoin, Phenobarbitone, Carbamazepine and Sodium Valproate in Epileptic Patients Attending a Tertiary Care Hospital

Jagennath

Raj

Mathaiyan

2019

IJPI

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“…The females had 57 % samples in sub-therapeutic levels and males had only 36 % samples in sub-therapeutic levels. Sirmagul et al [19] reported that combination of phenytoin with CBZ results in higher concentration in men than women. Our potential explanation of these more number of sub-therapeutic samples in females may be due to poor compliance or pregnancy because decreased plasma levels possibly due to increased metabolism of CBZ in pregnancy.…”

mentioning

confidence: 99%

Measurement and Comparison of Carbamazepine Plasma Levels for Assessment of Compliance, Safety and Toxicity

Shaikh¹,

Guo²

2017

pharmaceutical-sciences

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Shaikh and Guo: Measurement of Carbamazepine plasma levelsCarbamazepine is one of the most frequently prescribed antiepileptic drugs and influence of genetic differences, sex, age and race on the plasma levels of carbamazepine and its metabolites is well known. The objective of this study was to assess and compare the compliance, safety and toxicity in different age and gender groups of Chinese epileptic patients on the basis of therapeutic drug monitoring results of carbamazepine, since Han-Chinese are at higher risk of developing serious and fatal adverse effects when exposed to carbamazepine. The therapeutic drug monitoring results of carbamazepine in epileptic patients, obtained with validated methods were complied, evaluated and compared for compliance, safety and toxicity in different age and gender groups of Chinese epileptic patients. The therapeutic drug monitoring results of males and females were separately compiled and thereafter each gender group was further divided into children, adults and elderly as different age group. All age groups in both gender groups were evaluated for therapeutic, sub-therapeutic and toxic ranges. It was found that 45 % of samples of total samples had sub-therapeutic levels and 55 % of all samples had carbamazepine levels in therapeutic range, and none of gender and age group found in toxic range. Compared to males, female samples were more in number of sub-therapeutic levels. Populations of children males and children females were having more samples in sub-therapeutic levels as compared to adult and elderly males and females, respectively. However, it needs further evaluation. The findings of present study revealed that majority of patients were in sub-therapeutic levels. It is suggested that regularly therapeutic drug monitoring of carbamazepine should be performed and dose of carbamazepine in epileptic patients should be adjusted only after therapeutic drug monitoring results in order to assess the compliance, optimize the efficacy, safety and minimize the toxicity.

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“…TDM determines an individual reference concentration and improve treatment safety and efficacy. 12 Thus, several measurement methods were reported for optimizing the analytical signal, increasing sensitivity and selectivity of the determination of AEDs. 13 Efforts on developing analytical methods for quantification of AEDs in biological samples are ongoing.…”

Section: Discussionmentioning

confidence: 99%

Simultaneous Determination of Phenobarbital, Phenytoin, Carbamazepine and Carbamazepine-10,11-epoxide in Plasma of Epileptic Patients

et al. 2019

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IntroductionAntiepileptic drugs (AEDs) are a group of drugs used to treat neurological disorder such as epilepsy, neuropathic pain, and migraine. Epilepsy is a common and diverse set of chronic neurological disorders. It is characterized by seizures affecting about 1% of the population. 1,2 The pharmacotherapy with AEDs is the first choice for the treatment of epilepsy as it controls the occurrence of unpredictable epileptic seizures on approximately two thirds of the patients. 3 Approximately 30-40% of patients do not achieve seizure control with a single AED and rational polytherapy with the goal of finding combinations of AEDs that have favorable characteristics, has become of greater importance. 4 Before that one should ensure that the drug has reached its therapeutic range and there is no possibility to increase its daily dose. The first generation AEDs (phenobarbital (PB), phenytoin (PHT) and carbamazepine (CBZ)) have been widely used to treat epilepsy. Because of their narrow therapeutic range in adults (10-40 µg mL -1 , 5-20 µg mL -1 and 2-12 µg mL -1 , respectively for PB, PHT and CBZ) 5 and their complex pharmacokinetic properties, their blood levels should be monitored. Therapeutic ranges of PB, PHT and CBZ in children are 20-60 µg mL -1 , 3 6-11 µg mL -1 6 and 4-12 µg mL -1 , 7 respectively. Lethal concentrations of PB and PHT are 50 µg mL -1 for both drugs 5 and fatalities could be observed in CBZ serum concentrations of >20 µg mL -1 5 or >39 µg mL -1 . 8 CBZ is metabolized to its metabolite, i.e. carbamazepine-10, 11epoxide (CBZE), or simply the "epoxide" metabolite. The presence of this metabolite can have clinically significant implications in therapeutic drug monitoring (TDM) of CBZ. In addition, toxic symptoms may occur when plasma concentration of CBZE is >3.2 µg mL -1 . Thus CBZE quantification is importance in patients where CBZ has been ingested. 9,10 When each one of these three drugs fails to control seizures, a combination of the two most effective among them can be used. If the combination of CBZ and PHT fails, a combination of PB with CBZ or PHT would then become a consideration. 11 Drug A B S T R A C TBackground: Quantitative analyses of antiepileptic drugs are required in clinic and to rational dosage adjustment, the clinician needs the blood levels of these drugs. A highperformance liquid chromatography with spectrophotometric detection has been developed and validated for simultaneous determination of some antiepileptic drugs in plasma of patients with epilepsy. Methods: A simple procedure based on deproteinization by acetonitrile was used for pretreatment of plasma samples. Liquid chromatographic analysis was carried out on a Nova-Pak® C18 analytical column, using a ternary mixture of potassium dihydrogen phosphate buffer (pH 6.0)-acetonitrile-2-propanol (63:22:15, v/v/v) as the mobile phase, at a flow rate of 1.0 mL min -1 . Results: Calibration curves were linear over a range of 1-40 µg mL -1 for phenobarbital, 1-30 µg mL -1 for phenytoin, 0.3-15 µg mL -1 for carbamazepine and 0....

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The effect of combination therapy on the plasma concentrations of traditional antiepileptics

Cited by 9 publications

References 36 publications

Factors Influencing Plasma Concentrations of Phenytoin, Phenobarbitone, Carbamazepine and Sodium Valproate in Epileptic Patients Attending a Tertiary Care Hospital

Factors Influencing Plasma Concentrations of Phenytoin, Phenobarbitone, Carbamazepine and Sodium Valproate in Epileptic Patients Attending a Tertiary Care Hospital

Measurement and Comparison of Carbamazepine Plasma Levels for Assessment of Compliance, Safety and Toxicity

Simultaneous Determination of Phenobarbital, Phenytoin, Carbamazepine and Carbamazepine-10,11-epoxide in Plasma of Epileptic Patients

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