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Fulltext Selected pharmacokinetic issues of the use of antiepileptic drugs and parenteral nutrition in critically ill patients

Salih MR, Bahari MB, Abd AY

Nutr J, 2010 Dec 31;9:71.
PMID: 21194458 DOI: 10.1186/1475-2891-9-71

OBJECTIVES: To conduct a systematic review for the evidence supporting or disproving the reality of parenteral nutrition- antiepileptic drugs interaction, especially with respect to the plasma protein-binding of the drug.
METHODS: The articles related to the topic were identified through Medline and PubMed search (1968-Feburary 2010) for English language on the interaction between parenteral nutrition and antiepileptic drugs; the search terms used were anti-epileptic drugs, parenteral nutrition, and/or interaction, and/or in vitro. The search looked for prospective randomized and nonrandomized controlled studies; prospective nonrandomized uncontrolled studies; retrospective studies; case reports; and in vitro studies. Full text of the articles were then traced from the Universiti Sains Malaysia (USM) library subscribed databases, including Wiley-Blackwell Library, Cochrane Library, EBSCOHost, OVID, ScienceDirect, SAGE Premier, Scopus, SpringerLINK, and Wiley InterScience. The articles from journals not listed by USM library were traced through inter library loan.
RESULTS: There were interactions between parenteral nutrition and drugs, including antiepileptics. Several guidelines were designed for the management of illnesses such as traumatic brain injuries or cancer patients, involving the use of parenteral nutrition and antiepileptics. Moreover, many studies demonstrated the in vitro and in vivo parenteral nutrition -drugs interactions, especially with antiepileptics.
CONCLUSIONS: There was no evidence supporting the existence of parenteral nutrition-antiepileptic drugs interaction. The issue has not been studied in formal researches, but several case reports and anecdotes demonstrate this drug-nutrition interaction. However, alteration in the drug-free fraction result from parenteral nutrition-drug (i.e. antiepileptics) interactions may necessitate scrupulous reassessment of drug dosages in patients receiving these therapies. This reassessment may be particularly imperative in certain clinical situations characterized by hypoalbuminemia (e.g., burn patients).

Matched MeSH terms: Anticonvulsants/blood
Changes in serum perampanel concentration profile after discontinuation of carbamazepine

Murugesu S, Okayama K, Yamamoto Y, Terada K, Takahashi Y

Epileptic Disord, 2020 Aug 01;22(4):455-461.
PMID: 32782230 DOI: 10.1684/epd.2020.1182

To evaluate changes in the pharmacokinetics of perampanel after discontinuation of carbamazepine. We enrolled 13 patients receiving perampanel who discontinued carbamazepine therapy between June 2016 and December 2018. Data on serum concentrations were obtained from the therapeutic drug monitoring database of the National Epilepsy Center (Shizuoka, Japan). To compare the pharmacokinetics of perampanel before and after discontinuation of carbamazepine, we determined the concentration/dose (CD) ratio of perampanel (serum level [ng/mL] divided by the dose [mg/kg]). The follow-up period was set to eight weeks following the discontinuation of carbamazepine therapy. The mean baseline CD ratio of perampanel was 1,247 ng/mL/mg/kg which increased markedly over time after discontinuation of carbamazepine, with a mean CD ratio at Weeks 1-2, Weeks 3-4, and Weeks 5-8 of 2,683, 3,914, and 4,220, respectively. At eight weeks, the mean CD ratio of perampanel had increased by 276%. Eleven patients developed adverse events, including dizziness, somnolence, irritability, and ataxia. Five of these 11 patients required perampanel dose reduction within eight weeks after discontinuation of carbamazepine. Two patients achieved seizure-free status at Weeks 5-8. The serum perampanel concentration began to increase from one week after discontinuation of carbamazepine, and continued to rise for eight weeks. Based on these findings, we recommend frequent monitoring of serum perampanel concentration for at least eight weeks after stopping carbamazepine therapy. Monitoring is required as a guide for dose adjustment in order to achieve a safe and effective therapeutic dose of perampanel.

Matched MeSH terms: Anticonvulsants/blood*
Practices associated with serum antiepileptic drug level monitoring at a pediatric neurology clinic: a Malaysian experience

Salih MR, Bahari MB, Hassali MA, Shafie AA, Al-Lela OQ, Abd AY, et al.

J Pharm Pract, 2013 Jun;26(3):192-7.
PMID: 22797836 DOI: 10.1177/0897190012451926

OBJECTIVES: To assess the practices associated with the application of therapeutic drug monitoring (TDM) for antiepileptic drugs (AEDs) in the management of children with structural-metabolic epilepsy.
METHODS: It was a retrospective chart review and included children aged ≥2 years old with structural-metabolic epilepsy, treated with AEDs, and received TDM. The data were extracted from the medical records.
RESULTS: Thirty-two patients were identified with 50 TDM assays. In two thirds of the assays, "check level" and "recheck level" were the reasons behind the requesting of serum level monitoring of AEDs. Knowledge of serum AED levels led to alterations in the management in 60% of the assays. Thirty-two (76%) pediatrician's actions were consistent with the recommendation of TDM pharmacist. Forty-nine (98%) levels were appropriately indicated. In relation to the appropriateness of sampling time, 9 (18%) levels were not assessed due to missing data. Twenty-seven (54%) levels were appropriately sampled.
CONCLUSIONS: More studies should be designed to improve the component of the current TDM request form, especially in the reason section. By the same token, the number of pointless assays and the costs to the health care system can be reduced both by enhancing and improving the educational standards of the requesting neurologists.
KEYWORDS: Malaysia; epilepsy; neurology; pediatrics; therapeutic drug monitoring
Study site: Paediatric Neurology Clinic, Hospital Pulau Pinang, Malaysia

Matched MeSH terms: Anticonvulsants/blood*

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