Impact of age, weight and concomitant treatment on lamotrigine pharmacokinetics.

WHAT IS KNOWN AND OBJECTIVE: Lamotrigine metabolism may be substantially altered with concomitant administration of valproic acid and/or carbamazepine. Such alterations may require the adjustment of lamotrigine dose to ensure optimal treatment efficacy and safety. METHODS: The extent of lamotrigine interactions was investigated dependent on age, gender, weight and dose of concomitant carbamazepine and/or valproic acid in 65 patients with epilepsy. Lamotrigine plasma steady-state oral clearance (CLss/F) and area under the curve (AUCss) were calculated from the dose of drug, average steady-state concentration (Css) and interval of administration. Multiple regression analysis was used for the identification and quantification of factors that influenced lamotrigine pharmacokinetics. RESULTS AND DISCUSSION: Age and dose of carbamazepine and valproic acid had significant influence on lamotrigine CLss/F and AUCss. Carbamazepine was associated with a dose-dependent increase and valproic acid with a dose-dependent decrease of lamotrigine metabolism rate. The effect of carbamazepine was more pronounced. Younger patients were expected to metabolize lamotrigine more rapidly whereas overweight patients may be less susceptible to interactions. Gender had no influence on lamotrigine pharmacokinetics. WHAT IS NEW AND CONCLUSION: The efficacy and safety of lamotrigine may be altered by concomitant administration of carbamazepine and valproic acid. The models developed may be useful for estimating doses of lamotrigine for individual patients to minimize clinically significant interactions. Therapeutic monitoring is advisable when those drugs are used concomitantly.

Topography of visual EEG reactivity in school-age children.

In order to quantify the visual reactivity of EEG to opening the eyes, the topography of EEG power spectra for a sample of 72 healthy subjects of age ranging from 7 to 15 years was investigated. The EEGs were recorded from 16 scalp sites with eyes open (EOP) and eyes closed (ECL). Ln-transformed absolute EEG powers, acquired under these two states, were tested with Wilcoxon's paired test for differences between the powers. The absolute powers in alpha band and in total, were significantly higher in all derivations, under the ECL, as compared with the EOP, condition. Absolute powers in theta band under the ECL condition were also significantly higher than those under the EOP condition, except for frontal derivations. Changes in delta power were insignificant. Beta 1 band activity, when eyes were closed, was maximal in posterior and minimal in anterior derivations. When the eyes were open, the greatest beta 1 power was found in the frontal derivations. Beta 2 was the only band in which a frequent increase in power took place with eyes opening. Eyes opening appeared to decrease significantly, the beta 1 and beta 2 powers only in posterior derivations. The results showed that the visual blocking of EEG was mostly due to a higher degree of EEG desynchronization for the subjects aged 7-5 years.

Computerized EEG topography of normal preadolescent twins--correlating similarity of background activity with genetic relatedness.

The influence of genetic relatedness on the similarity degree of topographical EEG parameters was studied in a sample of 26 sets of monozygotic (MZ) and 46 sets of dizygotic (DZ) twins. All 144 subjects were healthy, primary school children, aged 7-15 years, 69 boys and 75 girls. Correlation coefficients were calculated for 50 quantitative EEG parameters of paired values obtained at each of 16 active electrode sites, in four groups of paired tracings: 1. MZ twins, 2. DZ twins, 3. The autocorrelated (A) group formed by correlating the spectral parameters from the same subjects in two different analyzed sequences, 4. The random (R) control group of 1200 unrelated pairs formed from DZ twin pairs. Sets of MZ twins and A group showed the highest degrees of similarity of spectral parameters over all brain areas except for significant differences only for some background features over posterior regions. In contrast, highly significant differences in topographic parameters were evident in comparison of MZ sets with DZ sets, particularly when MZ sets were compared with DZ subsets of opposite sex. Both number and degree of significant differences increased progressively in comparisons with groups 3 vs 2, 1 vs 4, and 3 vs 4. The data gave strong evidence for a complex polygenic determination of normal human EEG topography.