A Comprehensive Overview of the Clinical Pharmacokinetics of Clobazam

Tolbert, Dwain; Larsen, Frank

doi:10.1002/jcph.1313

Cited by 20 publications

(14 citation statements)

References 63 publications

(204 reference statements)

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“…N-desmethylclobazam and its metabolites account for 94% of the total drug-related components in urine, while unchanged CLB accounts for 2%. 2,8 Even in the presence of renal dysfunction, the manufacturer does not recommend dosage adjustment in patients with mild or moderate impairment. 1 Roberts et al 9 found that CLB and NCLB concentrations did not reach "toxic" values in adults with end-stage renal disease.…”

Section: Discussionmentioning

confidence: 99%

Persistent Hypersomnolence Following Clobazam in a Child With Epilepsy and Undiagnosed CYP2C19 Polymorphism

Hamilton¹,

Shelton²,

Wheless³

et al. 2020

The Journal of Pediatric Pharmacology and Therapeutics

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We describe an 11-year-old female who presented with severe hypersomnolence after receiving 1 week of modest doses of clobazam (CLB). In reviewing the above case, we considered that the hypersomnolence could be related to a pharmacodynamic, pharmacokinetic, or pharmacogenomic issue associated with CLB or to a combination of these factors. Although serum concentrations of CLB and its active metabolite are sensitive to factors that affect cytochrome-dependent metabolism, drug-drug interactions were omitted as a cause of the hypersomnolence. Subsequent DNA analysis of the cytochrome P450 2C19 gene revealed the patient as *2/*2 genotype with poor metabolizer enzyme activity. Because genetic testing of all patients treated with CLB is currently not practical, CLB dose/concentration ratios and pharmacokinetic drug-drug interaction impact models may be indicated. Genetic testing should be considered when an adverse effect suggests the possibility of a polymorphism important to drug metabolism.

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Section: Discussionmentioning

confidence: 99%

Persistent Hypersomnolence Following Clobazam in a Child With Epilepsy and Undiagnosed CYP2C19 Polymorphism

Hamilton¹,

Shelton²,

Wheless³

et al. 2020

The Journal of Pediatric Pharmacology and Therapeutics

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“…CLB is mainly metabolized by cytochrome P450 enzymes. Its major metabolite, NDMCLB, is an active metabolite and has a longer half-life than the parent drug (59-74 h vs. 36-42 h, respectively), significantly contributing to CLB pharmacological activity [25]. This paper describes a rapid, reliable, and simple method for measuring CLB and its metabolite NDMCLB in human plasma and the time needed for sample analysis is only 15 min.…”

Section: Discussionmentioning

confidence: 99%

Determination of Clobazam and Its Major Metabolite N-desmethylclobazam in Human Plasma with High-Performance Liquid Chromatography

Isse

Mahmoud

2021

Analytica

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Clobazam (CLB) is a benzodiazepine that is used in many types of epilepsy. Although therapeutic drug monitoring (TDM) of CLB is not routine, there is evidence that TDM may be of value in conditions where pharmacokinetic alterations are suspected. Therefore, determination of both CLB and its active metabolite concentrations is essential for TDM. Herein, we present a simple and practical method for determination of CLB and N-desmethylclobazam (NDMCLB) in human plasma by high-performance liquid chromatography (HPLC). The drugs were extracted by hexane:dichloromethane (1:1, v/v) from 0.3 mL plasma. The separation was carried out with a C18 reverse phase column using a mobile phase of water:acetonitrile (57:43, v/v) pumped at 0.8 mL/min. The analytes were detected at 228 nm. The method was linear over the concentration range 20–500 ng/mL for CLB and 200–3000 ng/mL for NDMCLB. The intra-day coefficient of variation (CV) was <10% for CLB and <6% for NDMCLB, while the inter-day CV for CLB was <16%. The metabolite inter-day CV was <6%. The accuracy of intra- and inter-day assessments determined for CLB and NDMCLB was within ±10%. This paper describes a rapid, reliable, and simple method for measuring CLB and its metabolite NDMCLB in human plasma. This UV-HPLC procedure offers acceptable precision and accuracy to quantify CLB and its metabolite in human plasma.

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“…CLB represents linear pharmacokinetics. The therapeutic range for CLB is 0.03-0.30 mg/L and 0.3-3.0 mg/L for N-CLB [19,29,35,86]. The drug undergoes extensive metabolism in the liver to an active metabolite N-desmethylclobazam (N-CLB) and other metabolites (Table 1).…”

Section: Clobazammentioning

confidence: 99%

Pharmacokinetic Drug–Drug Interactions among Antiepileptic Drugs, Including CBD, Drugs Used to Treat COVID-19 and Nutrients

Karaźniewicz−Łada

Główka

Mikulska

et al. 2021

IJMS

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Anti-epileptic drugs (AEDs) are an important group of drugs of several generations, ranging from the oldest phenobarbital (1912) to the most recent cenobamate (2019). Cannabidiol (CBD) is increasingly used to treat epilepsy. The outbreak of the SARS-CoV-2 pandemic in 2019 created new challenges in the effective treatment of epilepsy in COVID-19 patients. The purpose of this review is to present data from the last few years on drug–drug interactions among of AEDs, as well as AEDs with other drugs, nutrients and food. Literature data was collected mainly in PubMed, as well as google base. The most important pharmacokinetic parameters of the chosen 29 AEDs, mechanism of action and clinical application, as well as their biotransformation, are presented. We pay a special attention to the new potential interactions of the applied first-generation AEDs (carbamazepine, oxcarbazepine, phenytoin, phenobarbital and primidone), on decreased concentration of some medications (atazanavir and remdesivir), or their compositions (darunavir/cobicistat and lopinavir/ritonavir) used in the treatment of COVID-19 patients. CBD interactions with AEDs are clearly defined. In addition, nutrients, as well as diet, cause changes in pharmacokinetics of some AEDs. The understanding of the pharmacokinetic interactions of the AEDs seems to be important in effective management of epilepsy.

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A Comprehensive Overview of the Clinical Pharmacokinetics of Clobazam

Cited by 20 publications

References 63 publications

Persistent Hypersomnolence Following Clobazam in a Child With Epilepsy and Undiagnosed CYP2C19 Polymorphism

Persistent Hypersomnolence Following Clobazam in a Child With Epilepsy and Undiagnosed CYP2C19 Polymorphism

Determination of Clobazam and Its Major Metabolite N-desmethylclobazam in Human Plasma with High-Performance Liquid Chromatography

Pharmacokinetic Drug–Drug Interactions among Antiepileptic Drugs, Including CBD, Drugs Used to Treat COVID-19 and Nutrients

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