Therapeutic drug monitoring of carbamazepine and its metabolite in children from dried blood spots using liquid chromatography and tandem mass spectrometry

Shokry, Engy; Villanelli, Fabio; Malvagia, Sabrina; Rosati, Anna; Forni, G; Funghini, Silvia; Ombrone, Daniela; Bona, Maria Della; Guerrini, Renzo; Marca, Giancarlo la

doi:10.1016/j.jpba.2015.02.045

Cited by 42 publications

(21 citation statements)

References 26 publications

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“…Two studies compared C dbs and C p of carbamazepine in patients with epilepsy to derive direct conversion formulae: Kong et al recommended C p = (0.89 × C dbs ) + 1.00 μg/mL and Linder et al recommended C p = 0.84 × C dbs . In contrast, Shokry et al suggested that C dbs was highly correlated with C p after adjusting for Hct levels in paediatric patients ( r 2 = 0.9502). The only PK study that used DBS sampling evaluated carbamazepine; the results demonstrated that total daily dose and gender were covariate factors of C p , whereas total daily dose was the only factor of C dbs .…”

Section: Aed Concentration Measurement Using Dbs or Dpsmentioning

confidence: 89%

“…In 26 studies, 19 types of AEDs were measured using the DBS method 24,25,28,32,34, ; among them, 9 studies analysed >2 AEDs. 24,25,28,34,40,41,44,46,53 The most frequently analysed AED was carbamazepine (n = 8); others included lamotrigine (n = 7), valproic acid (n = 7), levetiracetam (n = 3), phenytoin (n = 3), topiramate (n = 3), carbamazepine epoxide (n = 2), gabapentin (n = 2), phenobarbital (n = 2), pregabalin (n = 2), clobazam (n = 1), clonazepam (n = 1), ethosuximide (n = 1), felbamate (n = 1), monohydroxycarbamazepine (n = 1), nitrazepam (n = 1), rufinamide (n = 1), vigabatrin (n = 1) and zonisamide (n = 1). Various analytical methods can be used to quantify the concentration of AEDs in DBS or DPS samples.…”

Section: Measurement Using Dbs or Dpsmentioning

confidence: 99%

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Development and clinical applications of the dried blood spot method for therapeutic drug monitoring of anti‐epileptic drugs

Min

Ryu

Chang

2019

Basic Clin Pharma Tox

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Anti‐epileptic drugs (AEDs) have various pharmacokinetic profiles, inter‐individual variabilities, high possibilities of drug‐drug interactions and narrow therapeutic indices. To provide optimal treatment for patients, therapeutic drug monitoring (TDM) is necessary. However, TDM requires sufficient quantities of blood samples to measure drug concentrations. Therefore, TDM could be a burden, particularly in paediatric cases. A good alternative that overcomes these disadvantages is the dried blood spot (DBS) method, which is simple, convenient to use and less invasive, requiring a lower quantity of blood than traditional blood sampling methods. However, the DBS method is affected by haematocrit (Hct) levels to varying extents depending on the drug properties. In addition, different papers with varying characteristics are available for use when applying the DBS method. Therefore, it has not yet been applied to TDM in clinical practice. To achieve this, several steps are required, including method development, method validation and clinical validation. Currently, the development status of the DBS method is different for each AED and unclear. Therefore, we assessed the development status of the following 19 AEDs in 26 studies: lamotrigine, valproic acid, levetiracetam, phenytoin, topiramate, carbamazepine, carbamazepine epoxide, gabapentin, phenobarbital, pregabalin, clobazam, clonazepam, ethosuximide, felbamate, monohydroxycarbamazepine, nitrazepam, rufinamide, vigabatrin and zonisamide. Among them, carbamazepine, lamotrigine, topiramate and valproic acid have been developed such that they are nearly available for TDM. In addition, Whatman 903 Protein Saver Cards and concentration analysis by liquid chromatography with triple quadrupole mass spectrometer were used most often.

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Section: Aed Concentration Measurement Using Dbs or Dpsmentioning

confidence: 89%

Section: Measurement Using Dbs or Dpsmentioning

confidence: 99%

Development and clinical applications of the dried blood spot method for therapeutic drug monitoring of anti‐epileptic drugs

Min

Ryu

Chang

2019

Basic Clin Pharma Tox

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“…13 Efforts on developing analytical methods for quantification of AEDs in biological samples are ongoing. [14][15][16][17][18][19][20] A number of factors should be taken into account in TDM of drugs in pediatrics. Differences exist in the pharmacokinetic behavior of drugs between children and adults, also between children in various development steps, and in many cases pediatrics drug dosage is scheduled based on personal experience of the pediatrician.…”

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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“…Because CBZ is lipid soluble, it slowly breaks down in the gastrointestinal (GI) fluid. CBZ is metabolized in the liver, forming several metabolites including carbamazepine-10,11-epoxide [35,63]. Only 1% of CBZ is excreted in urine unchanged [59].…”

Section: Discussionmentioning

confidence: 99%

The Influence of Solid Microneedles on the Transdermal Delivery of Selected Antiepileptic Drugs

et al. 2016

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The aim of this project was to examine the effect of microneedle rollers on the percutaneous penetration of tiagabine hydrochloride and carbamazepine across porcine skin in vitro. Liquid chromatography-mass spectrometric analysis was carried out using an Agilent 1200 Series HPLC system coupled to an Agilent G1969A TOF-MS system. Transdermal flux values of the drugs were determined from the steady-state portion of the cumulative amount versus time curves. Following twelve hours of microneedle roller application, there was a 6.74-fold increase in the percutaneous penetration of tiagabine hydrochloride (86.42 ± 25.66 µg/cm2/h) compared to passive delivery (12.83 ± 6.30 µg/cm2/h). For carbamazepine in 20% ethanol, passive transdermal flux of 7.85 ± 0.60 µg/cm2/h was observed compared to 10.85 ± 0.11 µg/cm2/h after microneedle treatment. Carbamazepine reconstituted in 30% ethanol resulted in only a 1.19-fold increase in drug permeation across porcine skin (36.73 ± 1.83 µg/cm2/h versus 30.74 ± 1.32 µg/cm2/h). Differences in flux values of untreated and microneedle-treated porcine skin using solid microneedles for the transdermal delivery of tiagabine were statistically significant. Although there were 1.38- and 1.19-fold increases in transdermal flux values of carbamazepine when applied as 20% and 30% ethanol solutions across microneedle-treated porcine skin, respectively, the increases were not statistically significant.

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Therapeutic drug monitoring of carbamazepine and its metabolite in children from dried blood spots using liquid chromatography and tandem mass spectrometry

Cited by 42 publications

References 26 publications

Development and clinical applications of the dried blood spot method for therapeutic drug monitoring of anti‐epileptic drugs

Development and clinical applications of the dried blood spot method for therapeutic drug monitoring of anti‐epileptic drugs

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

The Influence of Solid Microneedles on the Transdermal Delivery of Selected Antiepileptic Drugs

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