Relationship between mono-hydroxy-carbazepine serum concentrations and adverse effects in patients on oxcarbazepine monotherapy

Sattler, Annika; Schaefer, Marion; May, Theodor W.

doi:10.1016/j.seizure.2015.07.018

Cited by 11 publications

(5 citation statements)

References 24 publications

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“…The average plasma concentration of MHD was 18.38 ± 8.98 μg/ml ( n = 424), but only one sample was lower than the LLOQ (0.3 μg/ml). Our clinical results for MHD were close to the results reported for patients who were seizure‐uncontrolled (Bouquie et al, 2010), but the studies suggested that it would be more risky for the patients whose monitoring concentrations were beyond the reference range owing to its fold‐increase risk with plasma (Voinescu & Pennell, 2015) concentrations over 35 μg/ml (Sattler et al, 2015; Striano et al, 2006). Patients whose plasma concentrations were beyond the therapeutic range of MHD (3‐35 μg/ml) were warned to be careful of drug adverse effects when requiring a downward change in drug dose (Patsalos et al, 2008).…”

Section: Resultssupporting

confidence: 84%

LC–MS/MS quantification of levetiracetam, lamotrigine and 10‐hydroxycarbazepine in TDM of epileptic patients

Zhou

Chen

et al. 2022

Biomedical Chromatography

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Background To minimize drug‐related toxicity and monitor dosing regimens, an ultra‐sensitive, simple and high‐throughput analytical method for therapeutic drug monitoring is required. A novel LC–MS/MS bioassay of levetiracetam, lamotrigine and 10‐hydroxycarbazepine in human plasma was established. The analytes were separated on a Hypersil GOLD™ C18 column under a 2.5 min isocratic elution after one‐step protein precipitation. MS detection was performed under electrospray ionization positive‐mode fitted with selected reaction monitoring. The validated ranges were 0.1–20 μg/ml for LTG, 0.3–60 μg/ml for 10‐hydroxycarbazepine and levetiracetam. The intra‐ and inter‐batches of precision and accuracy was within ±15%. The novel method met all other criteria. Conclusion: This method can be used to monitor drug concentrations and decision‐making in epileptic patients.

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Section: Resultssupporting

confidence: 84%

LC–MS/MS quantification of levetiracetam, lamotrigine and 10‐hydroxycarbazepine in TDM of epileptic patients

Zhou

Chen

et al. 2022

Biomedical Chromatography

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“…[17] The association between the SNPs and MHD remains unclear. A study in German patients found that younger patients may tolerate higher MHD serum levels and higher OXC dosages per body weight than adult patients, [18] whereas Sánchez had the opposite result in the association between ABCB1 polymorphisms and drug resistance in Caucasian patients. [19] Moreover, the clearances and distribution volumes of OXC and MHD were found to be related to patient weight.…”

Section: Introductionmentioning

confidence: 99%

Comparison of oxcarbazepine efficacy and MHD concentrations relative to age and BMI

et al. 2019

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“…In many patients, AEs occurred intermittently in relation to MHD concentration fluctuations. Sattler et al reported that the occurrence of AEs was significantly (and non‐linearly) dependent on MHD serum concentrations. At MHD serum level of 30.0 μg/mL and 43.7 μg/mL, 25% and 75% of patients respectively experienced at least one AE.…”

Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics and dose simulation of oxcarbazepine in Chinese paediatric patients with epilepsy

et al. 2019

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Summary What is known and objectives Oxcarbazepine (OXC) is a widely used antiepileptic drug whose effect mainly depends on its active metabolite 10‐hydroxycarbazepine (MHD). This study established a population pharmacokinetic (PPK) model of MHD in Chinese children with epilepsy and conducted a dosage simulation in order to provide support for individualized OXC treatment. Methods Ninety‐one plasma sampling points from 88 paediatric patients were retrospective collected. MHD concentrations were detected, and patients’ clinical data were recorded. PPK analysis was performed using a non‐linear, mixed‐effect modelling approach. The goodness‐of‐fit (GOF) plots, bootstrap method, prediction‐corrected visual predictive check (pcVPC) and normalized prediction distribution errors (NPDE) were performed to evaluate the final model. External model validations by an independent group of paediatric patients (10 patients, 10 blood samples) were conducted. The steady‐state trough concentrations of MHD were determined by Monte Carlo simulations for doses ranging from 8 to 60 mg/kg/day. Results A one‐compartment model with first‐order elimination successfully described the data. The typical values for MHD clearance (CL/F), distribution volume (V/F) and absorption rate constant (Ka) were 3.25 L/h/70 kg, 151.41 L/70 kg and 0.598 h−1, respectively. The CL/F and V/F of MHD were related to body weight (WT) via an empirical allometric model. Internal and external validations demonstrated a good predictability of the final model. Monte Carlo simulations revealed that for most paediatric patients, a dosing regimen of 20‐30 mg/kg/d bid maybe sufficient to reach MHD therapeutic range. What is new and conclusion A PPK model of MHD in Chinese paediatric patients was successfully established. A priori dosing guideline was proposed considering WT and MHD plasma concentrations, providing a basis for OXC dosage calculations and adjustments in Chinese epileptic children.

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Relationship between mono-hydroxy-carbazepine serum concentrations and adverse effects in patients on oxcarbazepine monotherapy

Abstract: The occurrence of AEs is significantly (and non-linearly) dependent on MHD serum level, whereas the dependence of OXC dosage is less distinctive. But, tolerability of OXC seems to depend on age of the patients as well as on pharmaceutical formulation of OXC.

Cited by 11 publications

References 24 publications

LC–MS/MS quantification of levetiracetam, lamotrigine and 10‐hydroxycarbazepine in TDM of epileptic patients

LC–MS/MS quantification of levetiracetam, lamotrigine and 10‐hydroxycarbazepine in TDM of epileptic patients

Comparison of oxcarbazepine efficacy and MHD concentrations relative to age and BMI

Population pharmacokinetics and dose simulation of oxcarbazepine in Chinese paediatric patients with epilepsy

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