ABSTRACT
ABSTRACT A simple and sensitive HPLC method was developed and validated for the quantification of haloperidol in solid lipid nanoparticles (SLNs). The developed method was used for detection of shelf life of haloperidol in SLNs. Calibration curve of haloperidol was also constructed in rat plasma using loratidine as internal standard. In vivo studies were performed on rats and concentration of haloperidol in brain and blood was measured for the determination of various pharmacokinetic and hence brain targeting parameters. Chromatogram separation was achieved using C18 column as stationary phase. The mobile phase consisted of 100 mM/L potassium dihydrogen phosphate-acetonitrile-TEA (10:90:0.1, v/v/v) and the pH was adjusted with o-phosphoric acid to 3.5. Flow rate of mobile phase was 2 mL/minute and eluents were monitored at 230 nm using UV/VIS detector. The method was validated for linearity, precision, accuracy, reproducibility, limit of detection (LOD) and limit of quantification (LOQ). Linearity for haloperidol was in the range of 1-16 µg/mL. The value of LOD and LOQ was found to be 0.045 and 0.135 μg/mL respectively. The shelf life of SLNs formulation was found to be 2.31 years at 4 oC. Various parameters like drug targeting index (DTI), drug targeting efficiency (DTE) and nose-to-brain direct transport (DTP) were determined for HP-SLNs & HP-Sol administered intranasally to evaluate the extent of nose-to-brain delivery. The value of DTI, DTE and DTP for HP-SLNs was found to be 23.62, 2362.43 % and 95.77% while for HP-Sol, values were 11.28, 1128.61 % and 91.14 % respectively.
Subject(s)
Animals , Male , Female , Rats , Chromatography, High Pressure Liquid/classification , Growth and Development , Nanoparticles/statistics & numerical data , Haloperidol/analysis , Haloperidol/pharmacokinetics , Plasma/metabolism , In Vitro Techniques/instrumentationABSTRACT
Sustained blood level with effective therapeutic blood level in psychotic patients in the range of usual therapeutic dose is favorable. To investigate where this sustained and effective therapeutic blood level and improve in bioavailability could be achieved by using haloperidol/transdermal gel formulation. In-vivo transdermal delivery of haloperidol was studied in rabbits comparing transdermal gel formulation containing 1, 8-cineole as penetration enhancer and oral tablet. Concentrations of haloperidol in plasma were measured by reverse phase HPLC. The pharmacokinetic parameters generated from this study were evaluated statistically using one-way analysis of variance [ANOVA]. The results showed that transdermal gel formulation increased rate and extent of absorption and improve bioavailability of haloperidol. The plasma concentrations of haloperidol were declined in biexponential fashion where the area under the curves and absorption rate C[max]/AUC elimination rate constant K[el], T[max], mean residence time [MRT], mean absorption time [MAT], and total clearance [CL[total]] were significantly different p < 0.05, but volume of distribution [V[d]] did not differ significantly p >0.05.The absolute bioavailability from the oral tablet, and the transdermal formulation was 38% and 57% respectively and highly significant P < 0.01. This study suggest that it is possible to achieve significant sustained therapeutic blood levels for longer time and also suggest that further human investigations of the transdermal dosage are warranted
Subject(s)
Animals, Laboratory , Haloperidol/pharmacokinetics , Administration, Cutaneous , Tablets , RabbitsABSTRACT
O autor fez uma extensa revisäo bibliográfica sobre os neurolépticos, em especial o haloperidol, bem como sobre as reaçöes extrapiramidais, com atençäo principal ao parkinsonismo, com descriçäo de quadros e tratamentos indicados
Subject(s)
Humans , Male , Female , Antipsychotic Agents/pharmacokinetics , Antipsychotic Agents/therapeutic use , Biperiden/pharmacokinetics , Biperiden/therapeutic use , Parkinson Disease/drug therapy , Extrapyramidal Tracts/drug effects , Haloperidol/pharmacokinetics , Haloperidol/therapeutic useABSTRACT
Objetivo: Revisar las características del antipsicótico atípico olanzapina y analizar los estudios de eficacia clínica disponibles hasta ahora. Método: Se seleccionaron los trabajos más relevantes, los que fueron analizados desde el punto de vista de la eficacia clínica y de la seguridad del fármaco. Resultados: La olanzapina demostró eficacia sobre los síntomas positivos, negativos y depresivos de la esquizofrenia, mejorando la calidad de vida y disminuyendo las rehospitalízaciones. Tuvo escasos efectos colaterales y se asoció significativamente menos con la aparición de síntomas extrapiramidales y disquinesía tardía en comparación con el haloperidol. Conclusiones: La olanzapina parece representar una alternativa eficaz y segura para el tratamiento de la sintomatología esquizofrénica
Subject(s)
Humans , Antipsychotic Agents/pharmacokinetics , Schizophrenia/drug therapy , Clozapine/pharmacokinetics , Haloperidol/pharmacokinetics , Risperidone/pharmacokinetics , Psychotic Disorders/drug therapyABSTRACT
La hipótesis glutamatérgica de la esquizofrenia, que está recién en sus inicios, plantea que existe una alteración de la neurotransmisión glutamatérgica en esta enfermedad. La hipótesis se basa en los efectos psicoticomiméticos de la fenciclidina (PCF) y en las evidencias de actividad glutamatérgica anormal en pacientes esquizofrénicos. En este artículo se discute la posibilidad de que una deficiencia en la actividad de vías glutamatérgicas corticoestriatales pueda tener un papel fisiopatológico importante en la esquizofrenia. Se analizan las estrategias terapéuticas que se derivan de la hipótesis, como el empleo de agonistas glutamatérgicos y otros fármacos que pueden corregir la anormalidad planteada
Subject(s)
Humans , Glutamic Acid/deficiency , Dopamine/pharmacokinetics , Schizophrenia/physiopathology , Glutamic Acid/pharmacokinetics , Drug Interactions/physiology , Haloperidol/pharmacokinetics , Phencyclidine/adverse effects , Psychoses, Substance-Induced , Schizophrenia/drug therapyABSTRACT
Los neurolépticos (fenotiacinas) y otros medicamentos afines como el haloperidol y la metoclopramida, son causa frecuente de intoxicaciones cuyas principales manifestaciones son síntomas extrapiramidales. En su mayoría las intoxicaciones son de evolución aguda y en casos de grandes sobredosificaciones pueden complicarse con choque, coma y fibrilación ventricular; un signo de mal pronóstico es la hipertermia persistente. Su uso crónico, aún a dosis terapéuticas puede ocasionar discinecias tardías de difícil manejo. Se destaca la utilidad de la difenhidramina para el tratamiento de la intoxicación aguda, administrada inicialmente por vía endovenosa lenta (1 mg/kg/dosis), para una vez remitidos los síntomas, continuar por la vía bucal por un mínimo de 72 horas. La prevención debe dirigirse al uso racional de estos medicamentos y a evitar su uso inadecuado, frecuentemente abuso, derivados de modas terapéuticas