Terapijsko praćenje lakozamida

master's thesis

• Title (english): Therapeutic drug monitoring of lacosamide
• Author: Snježana Košić
• Mentor: Mila Lovrić (mentor)
• Committee member: Mila Lovrić (predsjednik povjerenstva)
• Committee member: Lidija Bach-Rojecky (član povjerenstva)
• Committee member: Maja Ortner Hadžiabdić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; Zagreb
• Defense date and country: 2021-03-18, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Lakozamid je moderni antiepileptik koji se koristi kao monoterapija ili dodatna terapija u liječenju parcijalnih
napadaja s ili bez sekundarne generalizacije u odraslih, adolescenata ili djece od navršenih 4 godina života. Prema
ILAE, koncentracije koje postižu optimalnu kontrolu bolesti za najveći broj bolesnika nalaze se u intervalu 10,0-40,0
μmol/L. Cilj rada bio je mjeriti i procijeniti koncentracije lakozamida u uzorcima seruma bolesnika na terapiji
antiepilepticima. Koncentracija lakozamida u stanju dinamičke ravnoteže određivana je na HPLC Prominence
Shimadzu uređaju uporabom internog standarda. Izmjerene koncentracije analizirane su prema spolu i dobi te je
dobiveno da spol i dob ne utječu na koncentraciju lakozamida, tj. da se koncentracije lakozamida ne razlikuju
statistički značajno između grupa suprotnog spola i grupa podijeljenih prema dobi: pedijatrijska populacija (mlađi < 7
godina), 7-18, 19-45, 46-65 godina i gerijatrijska populacija (stariji > 65 godina). Bolesnici su svrstani i u grupe prema
broju dodatnih antiepileptika u terapiji te prisustvu induktora i inhibitora enzima u politerapiji i analiza je pokazala da
se koncentracije lakozamida značajno razlikuju u bolesnika na politerapiji s induktorom/inhibitorom metabolizma.
Koncentracije lakozamida u politerapiji s induktorom metaboličkih enzima značajno su niže u odnosu na vrijednosti
bez induktora/inhibitora. 10 % ispitanih bolesnika, uz antiepileptik uzima i antidepresiv/ antipsihotik/ anksiolitik za
koje nije dokazan utjecaj na koncentracije lakozamida. Analiza koncentracija lakozamida u odnosu na preporučeni
referentni interval pokazala je da 70 % bolesnika postiže željene koncentracije.
Naši rezultati su pokazali da spol i dob nemaju utjecaj na koncentraciju lakozamida, ali vrsta ostale antiepileptičke
terapije (induktori/inhibitori) značajno utječe jer dovodi do promjena u farmakokinetici lakozamida pa je ukazana
potreba za individualizacijom terapije, odnosno terapijskim praćenjem lakozamida. Doza lakozamida određuje se za
svakog bolesnika prema dobi, BMI i funkciji bubrega, ali određivanje koncentracije lijeka koja omogućuje optimalnu
kontrolu terapije i minimalne neželjene pojave može značajno doprinijeti liječenju pogotovo u politerapiji s lijekovima
koji utječu na metabolizam.

Abstract (english)

Lacosamide is a modern antiepileptic drug used as monotherapy or adjunctive therapy in the treatment of partial
seizures with or without secondary generalization in adults, adolescents, or children from 4 years of age. According to
ILAE, the concentrations that achieve optimal disease control for most patients are in the range of 10.0-40.0 μmol / L.
The aim of this study was to measure and evaluate lacosamide concentrations in serum samples of patients on
antiepileptic therapy. Steady-state lacosamide concentration was determined on an HPLC Prominence Shimadzu
device using an internal standard. Measured concentrations were analyzed by sex and age and it was found that gender
and age did not affect lacosamide concentrations, ie that lacosamide concentrations did not differ statistically
significantly between groups of the opposite sex and groups divided by age: pediatric population (younger <7 years),
7-18, 19-45, 46-65 years and geriatric population (older> 65 years). Patients were also classified into groups according
to the number of additional antiepileptics in therapy and the presence of inducers and enzyme inhibitors in polytherapy
and the analysis showed that lacosamide concentrations differ significantly in patients on polytherapy with an inducer /
inhibitor of metabolism. Concentrations of lacosamide in polytherapy with an inducer of metabolic enzymes are
significantly lower compared to values without inducer / inhibitor. 10% of the examined patients, in addition to the
antiepileptic drug, also take an antidepressant / antipsychotic / anxiolytic for which no effect on lacosamide
concentrations has been proven. Analysis of lacosamide concentrations relative to the recommended reference interval
showed that 70% of patients achieved the desired concentrations.
Our results showed that gender and age do not affect the concentration of lacosamide, but the type of other
antiepileptic therapy (inducers / inhibitors) has a significant effect because it leads to changes in the pharmacokinetics
of lacosamide, so there is a need for individualization of therapy and therapeutic monitoring of lacosamide. The dose
of lacosamide is determined for each patient according to age, BMI and renal function, but determining the
concentration of the drug that allows optimal control of therapy and minimal side effects can significantly contribute
to treatment especially in polytherapy with drugs that affect metabolism.

• Keywords: epilepsija; antiepileptici; lakozamid; terapijsko praćenje; interakcije lijekova
• Keywords (english): epilepsy; antiepileptic drugs; lacosamide; therapeutic drug monitoring; drug interactions
• Language: croatian
• URN:NBN: urn:nbn:hr:163:619266
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-11-12 14:47:08