RESUMEN
A portable instrument has been developed for measuring silicon-containing aerosols in near real-time using laser-induced breakdown spectroscopy (LIBS). The instrument uses a vacuum system to collect and deposit airborne particulate matter onto a translatable reel of filter tape. LIBS is used to analyze the deposited material, determining the amount of silicon-containing compounds present. In laboratory testing with pure silica (SiO2), the correlation between LIBS intensity for a characteristic silicon emission and the concentration of silica in a model aerosol was determined for a range of concentrations, demonstrating the instrument's plausibility for identifying hazardous levels of silicon-containing compounds.
RESUMEN
This is the first study of the effect of topiramate on linguistic behavior and verbal recall using a computational linguistics system for automated language and speech analysis to detect and quantify drug-induced changes in speech recorded during discourse-level tasks. Healthy volunteers were administered a single, 100-mg oral dose of topiramate in two double-blind, randomized, placebo-controlled, crossover studies. Subjects' topiramate plasma levels ranged from 0.23 to 2.81 µg/mL. We found a significant association between topiramate levels and impairment on measures of verbal fluency elicited during a picture description task, correct number of words recalled on a paragraph recall test, and reaction time recorded during a working memory task. Using the tools of clinical pharmacology and computational linguistics, we elucidated the relationship between the determinants of a drug's disposition as reflected in plasma concentrations and their impact on cognitive functioning as reflected in spoken language discourse.
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Fructosa/análogos & derivados , Memoria a Corto Plazo/efectos de los fármacos , Recuerdo Mental/efectos de los fármacos , Habla/efectos de los fármacos , Aprendizaje Verbal/efectos de los fármacos , Adolescente , Adulto , Estudios Cruzados , Método Doble Ciego , Femenino , Fructosa/sangre , Fructosa/farmacología , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Tiempo de Reacción/efectos de los fármacos , TopiramatoRESUMEN
Carbamazepine is a widely prescribed antiepileptic drug. Owing to the lack of an intravenous formulation, its absolute bioavailability, absolute clearance, and half-life in patients at steady state have not been determined. We developed an intravenous, stable-labeled (SL) formulation in order to characterize carbamazepine pharmacokinetics in patients. Ninety-two patients received a 100-mg infusion of SL-carbamazepine as part of their morning dose. Blood samples were collected up to 96 hours after drug administration. Plasma drug concentrations were measured with liquid chromatography-mass spectrometry, and concentration-time data were analyzed using a noncompartmental approach. Absolute clearance (l/hr/kg) was significantly lower in men (0.039 ± 0.017) than in women (0.049 ± 0.018; P = 0.007) and in African Americans (0.039 ± 0.017) when compared with Caucasians (0.048 ± 0.018; P = 0.019). Half-life was significantly longer in men than in women as well as in African Americans as compared with Caucasians. The absolute bioavailability was 0.78. Sex and racial differences in clearance may contribute to variable dosing requirements and clinical response.
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Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/farmacocinética , Carbamazepina/administración & dosificación , Carbamazepina/farmacocinética , Epilepsia/tratamiento farmacológico , Epilepsia/metabolismo , Administración Oral , Adulto , Anticonvulsivantes/sangre , Disponibilidad Biológica , Carbamazepina/sangre , Química Farmacéutica , Epilepsia/sangre , Femenino , Semivida , Humanos , Infusiones Intravenosas/métodos , Masculino , Factores SexualesRESUMEN
BACKGROUND: Phenytoin (PHT) is widely used to treat epilepsy in elderly patients, but information on its pharmacokinetics in this population is limited. OBJECTIVE: The purpose of this study was to investigate the effects of age and sex on PHT pharmacokinetics using stable-labeled (SL) isotopes of PHT or fosphenytoin (FOS) administered IV or IM while patients remained on their oral maintenance regimen. METHODS: Subjects were patients 18 years or older with epilepsy, but otherwise healthy, on a maintenance regimen of PHT who were not taking interacting medications. Subjects were given a single injection of a 100 mg dose of SL-PHT or SL-FOS followed by their usual morning PHT dose less 100 mg. Serial blood samples were collected up to 196 hours after the SL dose. Plasma PHT and SL-PHT concentrations were measured by a gas chromatographic-mass spectrometric assay. PHT pharmacokinetics were characterized using a population-based, nonlinear, mixed-effects model. RESULTS: Sixty-three subjects completed the study, 45 of whom were 65 years or older. There was no difference between adult and elderly or men and women in PHT clearance, distribution volume, and elimination half-life. The mean elimination half-life was 40 hours. CONCLUSIONS: Healthy elderly adults appear to have the same phenytoin (PHT) pharmacokinetics as younger adults. Reduced PHT dosage requirements may be due to age-related changes in patients' sensitivity to the therapeutic and toxic effects of the drug. The prolonged elimination half-life suggests that most patients can take PHT once daily and the time to reach steady-state may extend to 2-3 weeks.
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Anticonvulsivantes/farmacocinética , Epilepsia/tratamiento farmacológico , Fenitoína/farmacocinética , Administración Oral , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Envejecimiento/fisiología , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/sangre , Esquema de Medicación , Epilepsia/prevención & control , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Inyecciones Intramusculares , Inyecciones Intravenosas , Masculino , Tasa de Depuración Metabólica/fisiología , Persona de Mediana Edad , Fenitoína/administración & dosificación , Fenitoína/sangre , Factores SexualesRESUMEN
BACKGROUND: Levetiracetam (LEV) is a recently approved anticonvulsant with proven efficacy and safety in the treatment of partial seizures. LEV may cause behavioral abnormalities that can be severe and require discontinuation of this drug. Risk factors for discontinuing LEV have not been established. OBJECTIVE: To determine incidence of behavioral abnormalities severe enough to require discontinuation of LEV and identify risk factors for such behavioral abnormalities. METHODS: All patients treated with LEV at MINCEP between January 2000 and February 2002 constituted the study population (n = 553). Patients who had discontinued LEV for behavioral reasons were selected as index cases. Case controls were patients starting LEV immediately after the index case. Potential risk factors for LEV discontinuation included age, gender, cognitive function, history of psychiatric diagnosis, epilepsy syndrome, number of antiepileptic drugs, titration rate, maximum dose of LEV, and LEV level at maximum dose. RESULTS: Thirty-eight patients (6.9%) discontinued LEV because of behavioral abnormalities. Variables associated with LEV discontinuation included faster titration rate to maximal dose, history of a psychiatric disorder, and diagnosis of symptomatic generalized epilepsy. Patients who discontinued LEV owing to behavioral reasons had significantly lower maximum LEV doses than controls. CONCLUSIONS: This study identified variables associated with discontinuation of LEV due to behavioral abnormalities. Slower titration of LEV should be considered in those patients at higher risk of discontinuing LEV for behavioral reasons.
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Anticonvulsivantes/efectos adversos , Síntomas Conductuales/inducido químicamente , Piracetam/análogos & derivados , Piracetam/efectos adversos , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Niño , Relación Dosis-Respuesta a Droga , Epilepsia/tratamiento farmacológico , Femenino , Humanos , Incidencia , Levetiracetam , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Factores SexualesRESUMEN
OBJECTIVE: To determine incidence of and risk factors for sudden unexpected death in epilepsy (SUDEP). METHODS: Three epilepsy centers enrolled 4,578 patients and prospectively followed these patients for 16,463 patient-years. The cohort was screened for death annually. Deaths were investigated to determine whether SUDEP occurred. Potential risk factors were compared in SUDEP cases and in controls enrolled contemporaneously at the same center. RESULTS: Incidence of SUDEP was 1.21/1,000 patient-years and was higher among women (1.45/1,000) than men (0.98/1,000). SUDEP accounted for 18% of all deaths. Occurrence of tonic-clonic seizures, treatment with more than two anticonvulsant medications, and full-scale IQ less than 70 were independent risk factors for SUDEP. The number of tonic-clonic seizures was a risk factor only in women. The presence of cerebral structural lesions and use of psychotropic drugs at the last visit were not risk factors for SUDEP in this cohort. Subtherapeutic anticonvulsant levels at the last visit were equally common in the two groups. No particular anticonvulsant appeared to be associated with SUDEP. CONCLUSIONS: These results support the idea that tonic-clonic seizures are an important proximate cause of SUDEP. This information creates a risk profile for SUDEP that may help direct preventative efforts.
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Muerte Súbita/epidemiología , Muerte Súbita/etiología , Epilepsia/complicaciones , Epilepsia/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Causas de Muerte , Niño , Preescolar , Estudios de Cohortes , Métodos Epidemiológicos , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
STUDY OBJECTIVE: To conduct a population pharmacokinetic analysis of carbamazepine (CBZ). DESIGN: Retrospective chart review. SETTING: Ambulatory neurology clinics at three medical centers. PATIENTS: Patients diagnosed with epilepsy from 1991-1995. The index set included 829 adults receiving CBZ. A separate validation set consisted of 50 patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Final regression equations were apparent oral clearance (Cl/F) (L/hr) = (0.0134 x TBW + 3.58), x 1.42 if receiving phenytoin only; x 1.17 if receiving phenobarbital or felbamate; x 1.62 if receiving phenytoin and phenobarbital or felbamate; x 0.749 if age > or = 70 years; apparent volume of distribution (Vd/F) (L) = 1.97 x total body weight; absorption rate constant [hr(-1)] = 0.441. Interindividual variability in Cl/F and Vd/F was 26% and 82%, respectively. Residual variability was 1.8 mg/L. Predictive performance analysis of the validation set provided a mean prediction error of 0.6 mg/L and median absolute error of 2.4 mg/L. CONCLUSIONS: These routinely collected data provided quantitative estimates of changes in CBZ Cl/F due to comedication and an age-related decrease in Cl/F The derived regression equations reasonably predicted concentrations in a separate validation set.