The relationship between UGT1A4 polymorphism and serum concentration of lamotrigine in patients with epilepsy

Lamotrigine (LTG) which has a widespread use in epilepsy treatment as an antiepileptic agent is metabolized by UDP-glucuronosyl transferase (UGT) enzymes. In this study, single nucleotide polymorphisms, P24T and L48V, of the UGT1A4 enzyme have been investigated in a Turkish population of patients with epilepsy (n=131) by comparing serum levels of LTG of wild type and polymorphic subjects

Pharmacologically induced absence seizures versus kindling in Wistar rats

WOS: 000514812200005PubMed: 32232200OBJECTIVE: This study aimed to investigate the effects of gamma-butyrolactone (GBL), a prodrug of gamma-Hydroxybutyric acid-induced absence seizures on the development of kindling in Wistar rats. METHODS: Three groups of adult male Wistar rats under anesthesia were implanted with bilateral cortical recording elec- trodes for the GBL group (GBL) and/or bipolar stimulation electrodes into the right basolateral amygdala for the Kindling group (KI) alone and Kindling plus GBL group (GBL+KI). Rats in the KI and GBL+KI groups were stimulated twice daily at the afterdischarge threshold until they reached Racine's stage 5 seizure state. the animals in the GBL + group had an i.p injection of GBL 20 minutes before each electrical stimulation, and the effects of GBL-induced seizures on the development of kindling were investigated. the animals in the GBL group were injected GBL twice daily i.p. for 15 days without receiving any electrical stimulation. RESULTS: the KI animals reached stage 5 seizure stage at 12th stimulations, whereas the GBL+KI rats reached at 27th stimulations. the mean numbers of stimulations needed for the development of the first stage 3, 4, or 5 generalized seizures were significantly higher in the GBL+KI group than the KI group. CONCLUSION: the resistance to amygdala kindling in the GBL model can be modulated by the absence seizure mechanism alone, without the intervention of an abnormal genetic background.Marmara University Research Council (BAPKO)Marmara University [SAG-D-300409-0116]This study was supported by Marmara University Research Council (BAPKO, SAG-D-300409-0116)

The effect of polymorphic metabolism enzymes on serum phenytoin level

Phenytoin has a widespread use in epilepsy treatment and is mainly metabolized by hepatic cytochrome P450 enzymes (CYP). We have investigated CYP2C9*2, CYP2C9*3, CYP2C19*2 and CYP2C19*3 allelic variants in a Turkish population of patients on phenytoin therapy. Patients on phenytoin therapy (n = 102) for the prevention of epileptic seizures were included. Polymorphic alleles were analyzed by restriction fragment length polymorphism method. Serum concentrations of phenytoin were measured by fluorescence polarization immune assay method. The most frequent genotype was detected for CYP2C9 wild-type alleles (78.43 %), whereas CYP2C19*2/*2 (5.88 %) was the least frequent genotype group. According to the classification made with both enzyme polymorphisms, CYP2C9*1/*1-CYP2C19*1/*1 (G1: 41.17 %) genotype group was the most frequent whereas CYP2C9*1/*2-CYP2C19*1/*3 (G7: 0.98 %) was the least frequent one. The highest mean phenytoin level (27.95 +/- A 1.85 A mu g/ml) was detected in the G8 genotype group (CYP2C9*1/*3-CYP2C19*2/*3) and the G1 genotype group showed the lowest mean phenytoin level (7.43 +/- A 0.73 A mu g/ml). The mean serum concentration of phenytoin of the polymorphic patients with epilepsy was higher than that for the wild-type alleles both in the monotherapy and polytherapy patients. These results show the importance of the genetic polymorphism analysis of the main metabolizing enzyme groups of phenytoin for the dose adjustment