Pharmacokinetic evaluation of vigabatrin dose for the treatment of refractory focal seizures in children using adult and pediatric data

Rodrigues, Christelle; Chiron, Catherine; Ounissi, Marwa; Dulac, Olivier; Gaillard, Ségolène; Nabbout, Rima; Jullien, Vincent

doi:10.1016/j.eplepsyres.2019.01.002

Cited by 6 publications

(2 citation statements)

References 51 publications

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“…The prescriber should be aware of the possible side effects, particularly potential retinal toxicity associated with peripheral vision loss, and how to monitor for these. While the risk of retinal toxicity or abnormalities on brain MRI may correlate with total cumulative dose, 101,102 improved control of infantile spasms also correlates with dose. 103,104 Therefore, the relative risks of uncontrolled epilepsy and treatment-related adverse effects should be discussed and weighed by health care providers and parents/ caregivers together.…”

Section: Epilepsymentioning

confidence: 99%

Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations

Northrup¹,

Aronow²,

Bebin³

et al. 2021

Pediatric Neurology

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Background: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease affecting multiple body systems with wide variability in presentation. In 2013, Pediatric Neurology published articles outlining updated diagnostic criteria and recommendations for surveillance and management of disease manifestations. Advances in knowledge and approvals of new therapies necessitated a revision of those criteria and recommendations. Methods: Chairs and working group cochairs from the 2012 International TSC Consensus Group were invited to meet face-to-face over two days at the 2018 World TSC Conference on July 25 and 26 in Dallas, TX, USA. Before the meeting, working group cochairs worked with group members via e-mail and telephone to (1) review TSC literature since the 2013 publication, (2) confirm or amend prior recommendations, and (3) provide new recommendations as required. Results: Only two changes were made to clinical diagnostic criteria reported in 2013: "multiple cortical tubers and/or radial migration lines" replaced the more general term "cortical dysplasias," and sclerotic bone lesions were reinstated as a minor criterion. Genetic diagnostic criteria were reaffirmed, including highlighting recent findings that some individuals with TSC are genetically mosaic for variants in TSC1 or TSC2. Changes to surveillance and management criteria largely reflected increased emphasis on early screening for electroencephalographic abnormalities, enhanced surveillance and management of TSCassociated neuropsychiatric disorders, and new medication approvals. Conclusions: Updated TSC diagnostic criteria and surveillance and management recommendations presented here should provide an improved framework for optimal care of those living with TSC and their families.

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Section: Epilepsymentioning

confidence: 99%

Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations

Northrup¹,

Aronow²,

Bebin³

et al. 2021

Pediatric Neurology

Self Cite

321

305

View full text Add to dashboard Cite

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“…Overall, this pooled analysis revealed that the racemic ketorolac EC 50‐racemic cannot simply be extrapolated between different populations when the pharmacological effect is only due to 1 specific enantiomer. Consequently, this analysis also serves as an example to not only focus on the changes in racemic ketorolac concentrations between populations, but also to reflect on the enantiomer‐specific contributions if relevant for a given compound 25 …”

Section: Discussionmentioning

confidence: 99%

Impact of enantiomer‐specific changes in pharmacokinetics between infants and adults on the target concentration of racemic ketorolac: A pooled analysis

Cloesmeijer

Esdonk

Lynn

et al. 2020

Brit J Clinical Pharma

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Ketorolac is a nonsteroidal anti-inflammatory racemic drug with analgesic effects only attributed to its S-enantiomer. The aim of this study is to quantify enantiomer-specific maturational pharmacokinetics (PK) of ketorolac and investigate if the contribution of both enantiomers to the total ketorolac concentration remains equal between infants and adults or if a change in target racemic concentration should be considered when applied to infants. Methods: Data were pooled from 5 different studies in adults, children and infants, with 1020 plasma concentrations following single intravenous ketorolac administration. An allometry-based enantiomer-specific population PK model was developed with NONMEM 7.3. Simulations were performed in typical adults and infants to investigate differences in Sand R-ketorolac exposure. Results: Sand R-ketorolac PK were best described with a 3-and a 2-compartment model, respectively. The allometry-based PK parameters accounted for changes between populations. No maturation function of ketorolac clearance could be identified. All model parameters were estimated with adequate precision (relative standard error <50%). Single dose simulations showed that a previously established analgesic concentration at half maximal effect in adults of 0.37 mg/L, had a mean S-ketorolac concentration of 0.057 mg/L, but a mean S-ketorolac concentration of 0.046 mg/L in infants. To match the effective adult S-ketorolac-concentration (0.057 mg/L) in typical infants, the EC 50-racemic should be increased to 0.41 mg/L. Conclusion: Enantiomer-specific changes in ketorolac PK yield different concentrations and Sand R-ketorolac ratios between infants and adults at identical racemic concentrations. These PK findings should be considered when studies on maturational pharmacodynamics are considered.

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Modulation of vigabatrin induced cerebellar injury: the role of caspase-3 and RIPK1/RIPK3-regulated cell death pathways

et al. 2021

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Pharmacokinetic evaluation of vigabatrin dose for the treatment of refractory focal seizures in children using adult and pediatric data

Cited by 6 publications

References 51 publications

Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations

Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations

Impact of enantiomer‐specific changes in pharmacokinetics between infants and adults on the target concentration of racemic ketorolac: A pooled analysis

Modulation of vigabatrin induced cerebellar injury: the role of caspase-3 and RIPK1/RIPK3-regulated cell death pathways

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