Brivaracetam population pharmacokinetics in children with epilepsy aged 1 month to 16 years

Schoemaker, Rik; Wade, Janet R.; Stockis, Armel

doi:10.1007/s00228-017-2230-6

Cited by 34 publications

(30 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…PK parameters in healthy participants are not significantly affected by age. 69 In participants aged >75 years, t ½ is slightly longer and clearance slightly lower compared with those aged 65–75 years; however, these changes are not considered significant enough to require a dose adjustment in elderly patients. 70…”

Section: Pharmacokinetic Profilementioning

confidence: 99%

“…72 In pediatric epilepsy patients, population PK analysis found that BRV exposure was reduced by 29% and 32% with concomitant administration of phenobarbital and carbamazepine, respectively, and increased by 11% with valproate. 69 …”

Section: Pharmacokinetic Profilementioning

confidence: 99%

“…Using data from this study, a population PK model of oral BRV in pediatric patients has been developed to provide guidance on dosing in the pediatric patient population. 69 Simulations demonstrated that with an age-independent dosing regimen of 2 mg/kg twice daily up to a maximum of 100 mg twice daily for body weight >50 kg, the majority of children were predicted to have an exposure similar to that in adult patients receiving 100 mg twice daily (the highest recommended dose).…”

Section: Efficacy Safety and Tolerability Of Adjunctive Brivaracetamentioning

confidence: 99%

See 2 more Smart Citations

A review of the pharmacology and clinical efficacy of brivaracetam

Klein¹,

Diaz²,

Gasalla³

et al. 2018

CPAA

View full text Add to dashboard Cite

Brivaracetam (BRV; Briviact) is a new antiepileptic drug (AED) approved for adjunctive treatment of focal (partial-onset) seizures in adults. BRV is a selective, high-affinity ligand for synaptic vesicle 2A (SV2A) with 15- to 30-fold higher affinity than levetiracetam, the first AED acting on SV2A. It has high lipid solubility and rapid brain penetration, with engagement of the target molecule, SV2A, within minutes of administration. BRV has potent broad-spectrum antiepileptic activity in animal models. Phase I studies indicated BRV was well tolerated and showed a favorable pharmacokinetic profile over a wide dose range following single (10–1,000 mg) and multiple (200–800 mg/day) oral dosing. Three pivotal Phase III studies have demonstrated promising efficacy and a good safety and tolerability profile across doses of 50–200 mg/day in the adjunctive treatment of refractory focal seizures. Long-term data indicate that the response to BRV is sustained, with good tolerability and retention rate. BRV is highly effective in patients experiencing secondarily generalized tonic–clonic seizures. Safety data to date suggest a favorable psychiatric adverse effect profile in controlled studies, although limited postmarketing data are available. BRV is easy to use, with no titration and little drug–drug interaction. It can be initiated at target dose with no titration. Efficacy is seen on day 1 of oral use in a significant percentage of patients. Intravenous administration in a 2-minute bolus and 15-minute infusion is well tolerated. Here, we review the pharmacology, pharmacokinetics, and clinical data of BRV.

show abstract

Section: Pharmacokinetic Profilementioning

confidence: 99%

Section: Pharmacokinetic Profilementioning

confidence: 99%

Section: Efficacy Safety and Tolerability Of Adjunctive Brivaracetamentioning

confidence: 99%

See 1 more Smart Citation

A review of the pharmacology and clinical efficacy of brivaracetam

Klein¹,

Diaz²,

Gasalla³

et al. 2018

CPAA

View full text Add to dashboard Cite

show abstract

“…A reason for these differences might be the methodology of the studies. The previous studies either used population PK modeling in adults 4 or children, 15 or investigated PK in healthy subjects 14 . In PK modeling, the effect of covariates on AED plasma clearance is estimated, which can be translated into other parameters, such as the change in average daily concentration.…”

Section: Discussionmentioning

confidence: 99%

Influence of dose and antiepileptic comedication on brivaracetam serum concentrations in patients with epilepsy

Hagemann¹,

Klimpel

Bien

et al. 2020

Epilepsia

View full text Add to dashboard Cite

The aim of this study was to investigate the influence of concomitant antiepileptic drugs (AEDs) on brivaracetam (BRV) trough serum concentrations. A total number of 368 routinely collected blood samples from 148 inpatients from Mara Hospital (Bethel Epilepsy Center) and von Bodelschwingh Foundation Bethel were retrospectively evaluated. Generalized estimation equations (GEEs) were used for statistical analysis. GEE analyses showed that BRV trough serum concentrations were significantly lower in patients with strong enzyme-inducing AEDs (carbamazepine, phenytoin, and/or phenobarbital/primidone, −49%), but were not affected by concomitant intake of oxcarbazepine or eslicarbazepine. Age and gender did not have a significant effect. An alternative GEE model analyzing the BRV level-to-dose ratios yielded comparable results. Our results from routine therapeutic drug monitoring data indicate that the effect of enzyme-inducing AEDs on BRV serum concentrations is stronger than the 20%-30% reduction in BRV exposure previously reported in pharmacokinetics studies. Further research is necessary to evaluate these differences and to elucidate possible clinical consequences. K E Y W O R D Santiepileptic drugs, brivaracetam, drug interactions, therapeutic drug monitoring e44 |

show abstract

“…В дальнейшем часть пациентов перешла в долгосрочное наблюдение, часть -закончила исследование с постепенным снижением дозы. Исследование N0 126 673 -долгосрочное исследование бриварацетама III фазы у пациентов в возрасте ≤17 лет -в настоящее время продолжается, и ожидается публикация о безопасности и переносимости бриварацетама у детей [17].…”

Section: Ch I Ld Neurology R U S S I a N J O U R N A L O Funclassified

Efficacy and tolerability of brivaracetam in the treatment of epilepsy: literature review and own experience

Пылаева¹,

Мухин²

2018

Rus. ž. det. nevrol.

View full text Add to dashboard Cite

Background. Despite significant advances in epileptology, approximately 30 % of patients suffer from drug-resistant epilepsy. Numerous approaches are currently available to treat epilepsy; however, there are still many patients with treatment-resistant disease, in whom surgery is impossible and alternative methods (vagus nerve stimulation and ketogenic diet) are ineffective. Thus, searching for new effective antiepileptic drugs (AED) for these patients remains highly relevant. In this article, we reviewed available publications and provided own results on the efficacy and tolerability of brivaracetam (Briviact®) in patients with intractable focal epilepsy.Materials and methods. The study included 8 patients aged between 16 and 35 years (mean age 18.3 years; 2 males and 6 females) with intractable focal epilepsy treated at the Svt. Luka’s Institute of Child Neurology and Epilepsy between February 1st, 2017 and September 1st, 2018.All patients received brivaracetam as an additional AED for the treatment of focal and bilateral convulsive seizures. Patients were followed up for 1 to 7.5 months. Brivaracetam was added to 1 or 2 AED (valproate, topiramate, or carbamazepine/oxcarbazepine) at a dose of 100–200 mg/day divided into 2 doses.Results and discussion. Good therapeutic effect (more than 50 % reduction in seizure frequency) was registered in 4 patients (50 %). Two patients (25 %) achieved a 25–50 % reduction in seizure frequency. Minimal clinical efficacy with no effect was observed in one patient (12.5 %). One patient (12.5 %) had aggravation of focal and motor seizures. Brivaracetam significantly reduced the severity (intensity and duration) of epileptic seizures in 70 % of patients. Four patients demonstrated substantial improvements on electroencephalogram (decreased epileptiform activity). One patient had complete suppression of epileptiform activity. Brivaracetam was most effective for bilateral convulsive seizures: 4 out of 5 patients experienced complete relief of these seizures.Brivaracetam demonstrated good tolerability: no side effects were registered in this study. Six out of 8 participants (75 %) currently continue treatment with brivaracetam. It is important that none of the patients had to stop brivaracetam due to poor tolerability. Of note, all of study participants started to receive brivaracetam because they had seizures resistant to multiple (more than 2–3) AED.Conclusion. Our findings suggest high efficacy and good tolerability of brivaracetam in patients with focal epilepsy. Our results are also consistent with the data reported by foreign authors.

show abstract

Brivaracetam population pharmacokinetics in children with epilepsy aged 1 month to 16 years

Cited by 34 publications

References 29 publications

A review of the pharmacology and clinical efficacy of brivaracetam

A review of the pharmacology and clinical efficacy of brivaracetam

Influence of dose and antiepileptic comedication on brivaracetam serum concentrations in patients with epilepsy

Efficacy and tolerability of brivaracetam in the treatment of epilepsy: literature review and own experience

Contact Info

Product

Resources

About