Leucine aminopeptidase isoenzyme changes after treatment with anticonvulsant drugs.
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A method is described to prepare routinely high resolution support-coated open tubular (SCOT) columns. A siliceous support material (Cab-O-Sil) is deactivated with benzyltriphenylphosphonium chloride and deposited on the inside wall of a glass capillary column. After additional coating with a polar stationary phase (OV-225) a number of anticonvulsant drugs can be analyzed without prior derivatization. The columns described show high plate numbers and do not deteriorate in use. The repeatability of the gas chromatographic analysis is better than 1.2% (Orel). The minimum detectable quantity is of the order of 10(-10) g. An improved procedure for isolating the drugs from serum is given, which results in an extraction recovery of better than 90% for the drugs of interest.
Fifty-five patients with intractable partial seizures whose on-medication EEGs demonstrated either predominantly focal epileptiform lesions or absence of paroxysmal activity, were studied, and the effect of withdrawing all anticonvulsive drugs on their EEGs was observed. Four types of response were encountered: (1) no effect (20%); (2) specific (focal) activation (25%); (3) complex activation (29%) with widespread of the initial on-medication focus or appearance of the additional independent epileptogenic foci; and (4) "non-specific" activation (63%), consisting of bursts of either bilaterally synchronous and frontally dominant spike and waves, triphasic waves, or sharp slow complexes, or smaller amplitude rapid and diffuse spike-and-wave complexes. This latter effect is thought to be secondary to metabolic derangements resulting from the withdrawal of neurotropic agents and not directly related to the specific epileptogenic process. No association was found between type of effect and any of the following parameters: topography of on-medication focus, duration of therapy, type of anticonvulsant used, suspected underlying etiopathology, or median age when medication was withdrawnn. Furthermore no evidence could be found that the development of a "complex" or "non-specific" EEG effect carried with it a bad prognosis for surgical cure following focal cortical excision. Performing off-medication tracings seems to be of greatest value in patients with partial seizures and EEGs revealing either a relative paucity of definite absence of epileptiform discharges. The occurrence of a "non-specific" response in a questionable epileptic during the off-medication period, on the other hand, should be interpreted with caution.
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Adolescence is a critical developmental period in which major metabolic changes occur. The majority of adolescents with epilepsy can be fully controlled with medications and can lead productive lives. A knowledge of basic principles of pharmacotherapy with AEDs will enable the physician to treat effectively most adolescents with epilepsy.
A method is described for the analysis of phenylethylmalonamide in human plasma. Analysis of plasma requires only 200 microliter of sample which is extracted with dichloroethane. After filtration and evaporation of the solvent the residue is reconstituted in 50 microliter of chloroform and 5 microliter are injected onto the gas chromatograph. The column used is a mixture of CDMS/WG11 coated on Chromosorb W HP 100-120 mesh. The method is suitable for use in single-dose pharmacokinetic studies.
We here present a method for the routine quantification of the novel antiepileptic drug levetiracetam in human serum by HPLC-UV. The procedure is very easy, quick, inexpensive and rugged. The sample preparation consists only in the precipitation of serum proteins by perchloric acid and extraction of unpolar components by cyclohexane. The aqueous phase containing the analyte levetiracetam is injected onto a porous graphitic carbon analytical HPLC-column and separated by gradient elution with diluted phosphoric acid/acetonitrile. Detection is carried out at a wavelength of 205 nm. The calibration function is linear in the range of 1-75 microg/ml. The detection limit is 0.1 microg/ml. Using four quality control sample concentrations, the inter-day relative standard deviations (R.S.D.) are lower than 3% and the accuracies are better than 6%. The respective inter-day values are: R.S.D. < 4% and accuracies better than 2%. Frequently co-administered antiepileptic drugs do not interfere with the assay. The method has been successfully applied to patient samples.
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