Combination of phenobarbital with phenytoin and pregabalin produces synergy in the mouse tonic-clonic seizure model: An isobolographic analysis.

AIMS: Despite many antiepileptic drugs (AEDs) are available to treat epilepsy, there is still about 30% of epilepsy patients inadequately treated with these AEDs. For these patients, polytherapy with two or three AEDs to fully control their seizure attacks is recommended. Unfortunately, polytherapy is always associated with drug interactions, whose nature may be beneficial, neutral or unfavorable. To determine a type of interaction for the combination of three AEDs (i.e., phenobarbital [PB], phenytoin [PHT] and pregabalin [PGB]) at the fixed-ratio of 1:1:1, we used a model of tonic-clonic seizures in male albino Swiss mice. MATERIALS AND METHOD: Tonic-clonic seizures in mice were evoked by a current (sine-wave, 25 mA, 500 V, 0.2 s stimulus duration) delivered via auricular electrodes. The anticonvulsant effects of the three-drug combination (PB, PHT and PGB) in terms of suppression of tonic-clonic seizures in mice were assessed with type I isobolographic analysis. Potential acute side effects for the mixture of PB, PHT and PGB along with total brain concentrations of the AEDs were determined to confirm pharmacodynamic nature of observed interaction. RESULTS: The three-drug combination of PB, PHT and PGB (at the fixed-ratio of 1:1:1) exerted synergistic interaction (at P < 0.01) in the mouse model of tonic-clonic seizures. The combination of PB, PHT and PGB did not produce any side effects in experimental animals, when measuring long-term memory, muscular strength and motor coordination. The measurement of total brain concentrations of PB, PHT and PGB was conducted to confirm that none of the three AEDs significantly influenced total brain concentrations (pharmacokinetic profiles) of the other co-administered AEDs in mice. CONCLUSIONS: The synergistic pharmacodynamic interaction for the combination of PB, PHT and PGB observed in this preclinical study can be translated into clinical settings and this favorable AED combination is worthy of being recommended to some patients with refractory epilepsy.

[Evaluation of the prognostic value of chosen maternal risk factors of complications existing among newborns of GDM mothers]. / Wartosc prognostyczna wybranych matczynych czynników ryzyka wystapienia powiklan u noworodków matek z cukrzyca ciazowa.

OBJECTIVES: According to WHO definition, gestational diabetes mellitus (GDM) is a disorder of carbohydrates tolerance during pregnancy. The incidence of GDM is about 2-4% in the population at pregnant women. Prematurity, neonatal dystrophy (particularly hypertrophy), hypoglycemia and other clinical abnormalities are more frequent in the group of the neonates of diabetic mothers. DESIGN: The aim of this study was to separate the maternal risk factors of complications existing among neonates of diabetic mothers as well as the statistical analysis of their prognostic values. MATERIAL AND METHODS: 260 newborns of GDM mothers, born at Polish Mothers Health Center were observed. The group of pregnant women was divided into two subgroups according to GDM class--G1 or G2. At 116 (44.6%) pregnant women glycemia was regulated dietetic treatment (G1 class). 144 women (55.4%) were treated with insulin (G2 class). The control group were 153 newborns from pregnant women with excluded GDM after carbohydrates tolerance screening test provide between 24-28 week. Estimation of the newborns status after birth was based on Apgar Score and umbilical blood pH. Basic laboratory tests were done in umbilical blood. Blood glucose concentration were monitored in all cases. Bilirubin concentration, infection screening tests were provided due to clinical status. Statistic evaluation was performed using special computer programs. CONCLUSIONS: G2 class of the Gestational Diabetes Mellitus significantly increases the frequency of newborn macrosomia, LGA, birth trauma, hypoglycemia, hyperbilirubinemia, cardiomyopathy and respiratory disorders. Prematurity is more frequent among newborns from GDM mothers group and it determines a potent risk factor of low Apgar Score, hypoglycemia and respiratory disorders. The following risk factors are unimportant for the frequency of complications existing among newborns of diabetic mothers: mothers age, number of delivers, obstetric complications and delivery of newborn with a congenital malformation in an anamnesis.