Clinical Pharmacokinetics of New-Generation Antiepileptic Drugs at the Extremes of Age: An Update

@article{Italiano2013ClinicalPO,
  title={Clinical Pharmacokinetics of New-Generation Antiepileptic Drugs at the Extremes of Age: An Update},
  author={Domenico Italiano and Emilio Perucca},
  journal={Clinical Pharmacokinetics},
  year={2013},
  volume={52},
  pages={627-645}
}
Epilepsies occur across the entire age range, and their incidence peaks in the first years of life and in the elderly. Therefore, antiepileptic drugs (AEDs) are commonly used at the extremes of age. Rational prescribing in these age groups requires not only an understanding of the drugs’ pharmacodynamic properties, but also careful consideration of potential age-related changes in their pharmacokinetic profile. The present article, which updates a review published in 2006 in this journal… 
Pharmacokinetic considerations for anti-epileptic drugs in children
TLDR
The main pharmacokinetic characteristics of AEDs used in children are reviewed, focusing on age-related factors which are of relevance when treating this patient population, especially in children.
Dosing strategies for antiepileptic drugs: from a standard dose for all to individualised treatment by implementation of therapeutic drug monitoring.
TLDR
There has been a shift in the view of treatment of epilepsy, from "one dose fits all patients" in the early days to individualisation of treatment, and knowledge of pharmacological variability of AEDs has markedly increased through implementation of therapeutic drug monitoring (TDM).
Pharmacokinetic characteristics of antiepileptic drugs (AEDs)
  • M. Marvanova
  • Medicine, Biology
    The mental health clinician
  • 2016
TLDR
This review discusses foundational pharmacokinetic characteristics of AEDs currently available in the United States, including clobazam but excluding the other benzodiazepines.
Pharmacokinetic Factors to Consider in the Selection of Antiseizure Drugs for Older Patients with Epilepsy
TLDR
Overall, the improved tolerability and decreased drug interaction potential of the newer-generation ASDs, such as lamotrigine and levetiracetam, have demonstrated their superiority in the treatment of seizures in older adults and, as such, are clearly favored for new-onset epilepsy in Older adults.
Pharmacokinetics and Drug Interaction of Antiepileptic Drugs in Children and Adolescents
TLDR
The mechanism of action, pharmacokinetics, drug–drug interactions, and safety/tolerability profiles of the main AEDs currently used in children and adolescents are reviewed, paying particular regard to issues of relevance when treating this patient population.
A Review of Population Pharmacokinetic Studies of Levetiracetam
TLDR
Lvetiracetam dose regimen is dependent on the body size and renal function of patients, and body weight was found to influence the apparent clearance and volume of distribution significantly, whereas renal function influenced the clearance.
Pharmacokinetic interactions and dosing rationale for antiepileptic drugs in adults and children
TLDR
The simulations show that DDIs can cause major changes in AED concentrations both in adults and children, and suggest that currently recommended dosing algorithms and titration procedures do not ensure attainment of appropriate therapeutic concentrations.
Effect of Age-Related Factors on the Pharmacokinetics of Lamotrigine and Potential Implications for Maintenance Dose Optimisation in Future Clinical Trials
TLDR
The availability of an integrated model including the whole patient population provides insight into the role of age-related changes in the disposition of lamotrigine, and potential implications for maintenance dose optimisation in any future trials.
Therapeutic drug monitoring of antiepileptic drugs: current status and future prospects
TLDR
An overview of the current evidence of the use and implementation of AED TDM in patients with epilepsy and other non-epilepsy conditions is provided to provide a quality assurance of the treatment.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 105 REFERENCES
Clinical Pharmacokinetics of New-Generation Antiepileptic Drugs at the Extremes of Age
  • E. Perucca
  • Medicine, Psychology
    Clinical pharmacokinetics
  • 2006
TLDR
Age-related CL/F changes, together with the large interindividual pharmacokinetic variability, contribute to the need for individualised dosage requirements in patients with epilepsy at the extremes of age and, for neonates and the elderly, alterations in drug binding to serum proteins.
Rufinamide in children with refractory epilepsy: pharmacokinetics, efficacy, and safety.
TLDR
In children neither on VPA nor on enzyme inducers, RUF clearance was age-dependent with higher clearance in younger children, and adding RUF did not change the pharmacokinetics of concomitant used AEDs.
Clinical Pharmacokinetics of Levetiracetam
  • P. Patsalos
  • Medicine, Biology
    Clinical pharmacokinetics
  • 2004
TLDR
The pharmacokinetic characteristics of levetiracetam are highly favourable and make its clinical use simple and straightforward and dosage adjustments are necessary for patients with moderate to severe renal impairment.
Pharmacokinetic Variability of Four Newer Antiepileptic Drugs, Lamotrigine, Levetiracetam, Oxcarbazepine, and Topiramate: A Comparison of the Impact of Age and Comedication
TLDR
Age had the greatest impact on levetiracetam, and comedication affected the clearance of each of the 4 AEDs investigated in this study, suggesting that age and Comedication are important contributors to pharmacokinetic variability.
Age-related changes in pharmacokinetics: predictability and assessment methods.
  • E. Perucca
  • Medicine, Biology
    International review of neurobiology
  • 2007
Developmental and Therapeutic Pharmacology of Antiepileptic Drugs
TLDR
The clinical effects of zonisamide (ZNS) were in agreement with the range of generally accepted therapeutic plasma levels of ZNS, 15–40 μg/ml, and a wide range of the plasma levels was associated with complete freedom from seizures.
The Pharmacology of New Antiepileptic Drugs
The year 2012 marks a milestone in the history of epilepsy, i.e. 100 years since phenobarbital was introduced for the treatment of seizure disorders. Despite bewildering advances in neuroscience in
The influence of age on the pharmacokinetics of the antiepileptic agent oxcarbazepine
TLDR
Accumulation of the pharmacologically active metabolite monohydroxycarbamazepine was found to be more than one would anticipate on the basis of linear and unchanged pharmacokinetics, and a significant higher maximum concentration, higher area under the curve parameters, and lower elimination rate constant were observed in the elderly.
...
1
2
3
4
5
...