Clobazam plasma concentrations: pharmacokinetic study in healthy volunteers and data in epileptic patients.

Tedeschi, G; Riva, R.; Baruzzi, Agostino

doi:10.1111/j.1365-2125.1981.tb01180.x

Cited by 35 publications

(18 citation statements)

References 7 publications

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“…mean). (Tedeschi et al, 1981;Greenblatt et al, 1983;Jawad et al, 1984). The last of these papers, however, described a shorter tma, (6-36 h) for NDMC derived from clobazam.…”

Section: Studymentioning

confidence: 99%

Pharmacokinetics of N‐desmethylclobazam in healthy volunteers and patients with epilepsy.

Pullar

Haigh

Peaker

et al. 1987

Brit J Clinical Pharma

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1 The single dose pharmacokinetics of N-desmethylclobazam (NDMC) and clobazam were studied in eight healthy male volunteers. 2 Steady-state pharmacokinetic data are described from four healthy male volunteers and eight epileptic patients taking NDMC.3 A single 30 mg dose of NDMC produced a greater Cma. (P < 0.001) and AUC 0-oo (P < 0.005) and a shorter tmax (P < 0.05) and tv½ (P < 0.01) for NDMC than did 30 mg clobazam. 4 Mean steady-state NDMC concentrations were greater in male patients than in female patients and also in male patients compared with male volunteers. The differences between patients and volunteers might be explained by concomitant antiepileptic medication.

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“…mean). (Tedeschi et al, 1981;Greenblatt et al, 1983;Jawad et al, 1984). The last of these papers, however, described a shorter tma, (6-36 h) for NDMC derived from clobazam.…”

Section: Studymentioning

confidence: 99%

Pharmacokinetics of N‐desmethylclobazam in healthy volunteers and patients with epilepsy.

Pullar

Haigh

Peaker

et al. 1987

Brit J Clinical Pharma

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“…injected into the chromatogram under the Plasma phenytoin and carbamazepine confollowing conditions: mobile phase 70:30 mix-centrations were measured using enzyme ture of K2H2PO4 (pH 6.8): acetonitrile; column: immunoassay (EMIT, Syva) in samples taken at the following times after clobazam administration -2, 4,6,12,24,72,96,144,192 values reported previously (Rupp et al, 1979;Tedeschi et al, 1981;Divoll et al, 1982). That induction of clobazam metabolism is the likely explanation for the above finding is supported by two observations: first, the elimination half-life of antipyrine in the epileptic patients was significantly reduced compared with the normal volunteers (Davies et al, 1973).…”

Section: Introductionmentioning

confidence: 99%

Single dose pharmacokinetic study of clobazam in normal volunteers and epileptic patients.

Jawad¹,

Richens²,

Oxley³

1984

Brit J Clinical Pharma

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1 The pharmacokinetics of clobazam were studied in six healthy volunteers and six age and sex matched enzyme-induced epileptic patients. 2 In the epileptic patients the area under the plasma concentration-time curve for clobazam was significantly smaller and the area under the plasma concentration-time curve for N-desmethylclobazam was significantly greater than in the healthy volunteers. 3 Plasma N-desmethylclobazam concentrations were found to be much higher than those of clobazam in the epileptic patients, raising the possibility that the antiepileptic properties of clobazam are to be attributed more to its metabolite than the parent drug.

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“…Further information on CLB PK and PopPK modeling was identified from unpublished reports from the drug sponsor and from references cited in the articles obtained in the literature search. In total, over 100 English‐language articles and abstracts were reviewed; 53 published and 3 unpublished reports were used to compile the information presented here on CLB PK, use in specific patient populations, drug interactions, and PopPK analyses …”

Section: Clobazam Clinical Pharmacokineticsmentioning

confidence: 99%

A Comprehensive Overview of the Clinical Pharmacokinetics of Clobazam

Tolbert

Larsen

2018

The Journal of Clinical Pharma

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Clobazam (CLB) is a 1,5‐benzodiazepine that has been widely used as an anxiolytic and antiseizure drug (ASD) since it was first synthesized over 50 years ago. CLB was approved in the United States in 2011 as adjunctive therapy for seizures in patients ≥2 years old with Lennox‐Gastaut syndrome. CLB pharmacokinetics (PK) have been studied in single‐ and multiple‐dose administrations in healthy subjects. Salient features include high bioavailability, linear PK, and negligible effects from coadministration of other ASDs. CLB is highly and extensively absorbed, with little effect from food; time to maximum plasma concentration is 0.5 to 4 hours following the dose. After CLB doses of 20 to 40 mg/day, the volume of distribution is 99 to 120 L, with oral clearance ranging from 1.9 to 2.3 L/h. CLB is lipophilic and distributes throughout the body after oral administration. It is metabolized in the liver by cytochrome P450 (CYP) isoenzymes CYP3A, CYP2C19, and CYP2B6, and its main active metabolite is N ‐desmethylclobazam. The half‐life of CLB after a single oral dose ranges from 36 to 42 hours; the half‐life of N ‐desmethylclobazam ranges from 59 to 74 hours. The metabolites of CLB are primarily excreted renally. Population PK modeling using data from healthy subjects and patients with Lennox‐Gastaut syndrome indicates that race, sex, age, weight, and renal function do not influence CLB PK. As CLB has been extensively studied since the 1970s, this review is meant to provide a consolidated and comprehensive resource on CLB PK for both prescribers and scientists alike.

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Clobazam plasma concentrations: pharmacokinetic study in healthy volunteers and data in epileptic patients.

Cited by 35 publications

References 7 publications

Pharmacokinetics of N‐desmethylclobazam in healthy volunteers and patients with epilepsy.

Pharmacokinetics of N‐desmethylclobazam in healthy volunteers and patients with epilepsy.

Single dose pharmacokinetic study of clobazam in normal volunteers and epileptic patients.

A Comprehensive Overview of the Clinical Pharmacokinetics of Clobazam

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