Rapid determination of piracetam in human plasma and cerebrospinal fluid by micellar electrokinetic chromatography with sample direct injection.

A simple micellar electrokinetic chromatography (MEKC) method with UV detection at 200 nm for analysis of piracetam in plasma and in cerebrospinal fluid (CSF) by direct injection without any sample pretreatment is described. The separation of piracetam from biological matrix was performed at 25 degrees C using a background electrolyte consisting of Tris buffer with sodium dodecyl sulfate (SDS) as the electrolyte solution. Several parameters affecting the separation of the drug from biological matrix were studied, including the pH and concentrations of the Tris buffer and SDS. Under optimal MEKC condition, good separation with high efficiency and short analyses time is achieved. Using imidazole as an internal standard (IS), the linear ranges of the method for the determination of piracetam in plasma and in CSF were all between 5 and 500 microg/mL; the detection limit of the drug in plasma and in CSF (signal-to-noise ratio=3; injection 0.5 psi, 5s) was 1.0 microg/mL. The applicability of the proposed method for determination of piracetam in plasma and CSF collected after intravenous administration of 3g piracetam every 6h and oral administration 1.2g every 6h in encephalopathy patients with aphasia was demonstrated.

Blood and cerebrospinal fluid pharmacokinetics of the novel anticonvulsant levetiracetam (ucb L059) in the rat.

The temporal pharmacokinetic interrelationship of levetiracetam in blood and cerebrospinal fluid (CSF) was studied after acute intraperitoneal administration of levetiracetam (20, 40 and 80 mg/kg), using an animal model that permits concurrent blood and CSF sampling in freely moving rats. After administration, levetiracetam rapidly appeared in both serum (time to maximum concentration (Tmax) mean range 0.25 0.50 h) and CSF (Tmax mean range 1.33-1.92 h), suggesting ready penetration of the blood brain barrier. Both serum and CSF levetiracetam concentrations rose essentially linearly and dose-dependently, suggesting that transport across the blood-brain barrier is not rate limiting over the levetiracetam concentration range observed in the present study. However, while apparent elimination half-life (t1/2) values for both serum and CSF were dose-independent (mean value range 1.8-2.8 and 4.4-4.9 h, respectively), t1/2 values for CSF were significantly larger. As the serum free/total serum levetiracetam concentration ratio (free fraction) was 1.01+/-0.02 (mean+/-S.E.M.), it can be concluded that levetiracetam is not protein bound. Furthermore, the free fraction was indistinguishable from that of the CSF/serum levetiracetam concentration ratio at equilibrium. It can be concluded that the kinetics of levetiracetam, in the rat, is simple and, thus, dosing strategies in studies designed to elucidate its mechanism of action should be straightforward.

Further assignment of resonances in 1H NMR spectra of cerebrospinal fluid (CSF).

A number of previously unidentified 1H NMR signals detected in CSF spectra of patients with various neurological and metabolic diseases are assigned to metabolites, drugs and drug excipients. Two-dimensional 1H NMR spectroscopy (COSY and J-resolved) is employed to resolve resonances which are hidden by superimposed peaks in one-dimensional spectra. Assignments obtained by making use of 2-D techniques, and of a 1-D 1H NMR data base created for ca. 150 authentic compounds, enable us to clarify the nature of complex signal patterns found in crowded spectral regions of CSF such as the aliphatic methyl region at ca. 1.0 ppm.

A high-performance liquid-chromatographic microanalytical procedure for the rapid estimation of piracetam in plasma or cerebrospinal fluid.

Presently available GC and HPLC methods for analysis of piracetam, require large samples and suffer from interference. A micro scale, isocratic high-performance liquid-chromatographic method is described for the determination of piracetam in plasma (25 microL) or cerebrospinal fluid (10 microL) using ultraviolet absorbance at 215 nm. The limit of quantitation is 4 micrograms mL-1 and the within-batch and between-batch coefficients of variation are less than 10%. No interference from other commonly prescribed antimyoclonic or antiepileptic drugs was observed and thus the method can be used to monitor piracetam in patients on polytherapy antimyoclonic or antiepileptic drug regimens. Because of the sensitivity and rapidity of the method it is suitable for pharmacokinetic and mechanistic studies and for analysis of paediatric samples.

El Piracetam en el Sindrome de abstinencia alcohólica / Piracetam in the Alcoholic withdrawal syndrome

Se efectuó un estudio abierto para apreciar la eficacia del piracetam en el síndorme agudo de la abstinencia alcohólica. Se estudiaron 30 pacientes varones con una edad promedio de 40 años y una crisis reciente de ingestión alcohólica de 17 días en promedio. La mayor parte eran consumidores de bebidas destiladas. 20 de estos pacientes tenían hospitalizaciones previas por alcoholismo; el registro de su respuesta a tratamientos anteriores pudo entonces servir de comparación para evaluar los resultados del tratamiento actual. 18 pacientes tuvieron alucinaciones y 2 desarrollaron un cuadro moderado de delirium tremens. La ansiedad y la agitación, así como los síntomas depresivos, fueron comunes. Durante 5 días, se administraron 9 gramos diarios de piracetam por vía endovenosa, fraccionados en tres dosis, y se evaluaron los signos y síntomas de los sujetos diariamente según una escala de 23 ítems clínicos. Dos pacientes abandonaron el ensayo antes de su fin. La apreciación general de los resultados fué favorable, destacándose la ausencia de somnolencia o letargia y l mayor vitalidad general en comparación con otros tratamientos. Para el quinto día, sólo 12 pacientes presentaban signos y síntomas ligeros de depresión y/o ansiedad. El piracetam parece superar a los fenotiazínicos y tener algunas ventajas sobre los benzadiazepínicos en el tratamiento de estos pacientes