RESUMO
The orally administered tablet and suspension of the analgesic drug nabumetone (Relafen), a novel naphthylalkanone, were tested for bioequivalence. Nabumetone is rapidly metabolized to an active metabolite, 6-methoxy-2-naphthylacetic acid (BRL 10720). The pharmacokinetics of the metabolite were studied in 24 healthy adult male volunteers. Each received a 1-g dose of the nabumetone formulations in a balanced, randomized, two-way crossover investigation. Serum metabolite concentrations were determined over a 120-hour interval by high-performance liquid chromatography. The values of the pharmacokinetic parameters computed for tablet and suspension are presented in that order: area under the curve = 1,269:1,338 mg.hour/ml; absorption half-life = 1.04:0.83 hour; elimination half-life = 27.16:25.15 hours; lag time = 0.19:0.07 hour; peak concentration = 27.56:31.91 micrograms/ml, and time to peak concentration = 4.99:4.17 hours. The mean concentration of BRL 10720 was found to be higher during the first eight hours for the suspension than for the tablet. Using criteria for statistical significance, the values for peak concentration, time to peak concentration, elimination half-life, and lag time were found significant (p less than 0.05). These results may well be reflecting the increased absorption characteristics of the suspension due to the pharmaceutical characteristics of the preparation. The formulations were found to be bioequivalent when compared on the premise that no significant difference was detected when area under the curve and all other parameters were compared, based upon the 75/75 rule analysis.
Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Butanonas/farmacocinética , Adulto , Anti-Inflamatórios não Esteroides/administração & dosagem , Butanonas/administração & dosagem , Humanos , Masculino , Nabumetona , Ácidos Naftalenoacéticos/farmacocinética , Suspensões , Comprimidos , Equivalência TerapêuticaRESUMO
Clavulanic acid is a beta-lactamase inhibitor which prevents microbial lactamase inactivation of beta-lactam antibiotics. The pharmacokinetics and urinary excretion of clavulanic acid were studied in eight healthy adult volunteers after oral administration of 500 mg amoxicillin and 125 mg potassium clavulanate. Serum and urine clavulanic acid concentrations were assayed using high-performance liquid chromatography. Pharmacokinetic parameters were: t 1/2 beta = 1.019 +/- 0.090 hour, t 1/2 alpha = 0.276 +/- 0.031 hour, lag time = 0.321 +/- 0.018 hour, tmax = 1.042 +/- 0.80 hour, Cmax = 2.098 +/- 0.441 micrograms/ml, and AUC = 4.897 +/- 0.979 micrograms X hr/ml. Cumulative urinary excretion of clavulanic acid (as percentage of dose administered) was: 14.05 +/- 2.87 within 2 hours, 25.77 +/- 3.98 within 4 hours, and 27.85 +/- 4.27 within 6 hours after administration.
Assuntos
Amoxicilina/metabolismo , Ácidos Clavulânicos/urina , Administração Oral , Adulto , Amoxicilina/administração & dosagem , Cromatografia Líquida de Alta Pressão , Ácido Clavulânico , Ácidos Clavulânicos/administração & dosagem , Feminino , Humanos , Cinética , MasculinoRESUMO
The plasma and red blood cell pharmacokinetics and bioavailability of the natural source (RRR, d) and all racemic (all rac, dl) stereoisomers of alpha-tocopherol were studied in 12 men in a double-blind randomized crossover study. Subjects were administered two 400-mg soft-gelatin capsules of either RRR or all rac alpha-tocopherol. Plasma alpha-tocopherol concentrations were determined by high-performance liquid chromatography at various time intervals for up to 96 hours postadministration. Pharmacokinetic modeling of the data showed that alpha-tocopherol was absorbed after a 2 to 4 hour lagtime and maximum plasma concentration occurred from 12 to 14 hours postadministration. There were no significant differences in the Ka, t1/2 a, beta, or t1/2 beta between RRR and all rac. Mean plasma alpha-tocopherol concentrations were greater for RRR than all rac from 10 to 96 hours postadministration and significantly greater at 24 hours (P < .05). The red blood cell alpha-tocopherol concentration from the RRR preparation was significantly greater than from the all rac preparation from 24 to 96 hours postadministration with Cmax for RRR (4.8 micrograms/mL) significantly greater than for all rac (4.0 micrograms/mL, P < .05). The RRR AUC0-96 for both plasma and red blood cells were significantly greater than the all rac AUC0-96 (P < .05) indicating a greater bioavailability of RRR versus all rac alpha-tocopherol. This difference in overall bioavailability was apparently not due to a single pharmacokinetic component.
Assuntos
Vitamina E/farmacocinética , Administração Oral , Adolescente , Adulto , Disponibilidade Biológica , Método Duplo-Cego , Humanos , Masculino , Estereoisomerismo , Vitamina E/administração & dosagem , Vitamina E/sangueRESUMO
The risk inherent in the clinical control of patients with theophylline is widely recognized. Elderly patients may present an additional risk because of altered pharmacokinetics and the use of concomitant medication. Acetylsalicylic acid has been proposed for primary and secondary prevention of myocardial infarction and possible strokes. This investigation was undertaken to determine if concomitant administration of acetylsalicylic acid in elderly patients would alter steady-state levels of theophylline. A population of smoking male patients older than 60 years of age under long-term control of chronic obstructive pulmonary disease (COPD) with theophylline were evaluated for a baseline period of 3 days. Serum levels were measured at 6:00 AM and 6:00 PM. An enteric-coated acetylsalicylic acid preparation, 650 mg by mouth, was added to the daily slow-release theophylline, 6:00 AM hour dose regimen for 4 weeks. The serum levels of theophylline and salicylates were measured at 6:00 PM after dosing and at 6:00 AM the following day, at weekly intervals for 4 weeks. Urine specimens collected before administration of medication at 6:00 AM were analyzed for salicylates to further confirm dosage compliance. All volunteers continued to be clinically controlled throughout the treatment period and no symptoms of either overdose or underdose of either medication occurred. Plateau or trough theophylline serum levels did not change significantly during the salicylate treatment period. Salicylate serum levels did show during treatment self-induced metabolism. It is concluded that in elderly male patients, a daily concomitant therapeutic salicylate regimen does not alter steady-state serum theophylline levels and therefore does not per se necessitate the assay of theophylline blood levels in elderly patients.
Assuntos
Aspirina/farmacologia , Rim/fisiologia , Teofilina/sangue , Idoso , Idoso de 80 Anos ou mais , Aspirina/administração & dosagem , Interações Medicamentosas , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Salicilatos/sangue , Salicilatos/urina , Comprimidos com Revestimento Entérico , Teofilina/administração & dosagem , Teofilina/metabolismoRESUMO
The osmotic fragility (OF) test is used to determine the extent of red blood cell hemolysis (RBCH) produced by osmotic stress. RBCH is dependent upon cell volume, surface area, and functional integrity of cell membranes. The variation of cell lysis with stress reflects underlying cell subpopulations and their membranes' cytoskeletal functionality. OF was determined on blood from New Zealand white rabbits. The dependence of RBCH on NaCl concentration ([NaCl]) was determined spectrophotometrically by measuring absorbance (Abs) from hemoglobin release at 545 nm. Abs data were fitted to the equation Abs = p3 erfc(([NaCl]--p1)/p2) where p3 reflects maximum RBCH, p1 measures the [NaCl] at 50% RBCH, and p2 shows the dispersion in [NaCl] producing the RBCH. Parameter values for control blood were p1 = 0.4489 +/- 0.0016; p2 = 0.0486 +/- 0.0016; and p3 = 0.4366 +/- 0.0022. Addition of indomethacin (9.6 micrograms/mL) produced an increased fragility in the RBC's characterized by increased values of p1 and p2. Normalization of the data to p3 did not change the values of p1 or p2. Our equation satisfactorily describes the variation in RBCH as a function of [NaCl]. The parameters of the equation can be used to quantitatively characterize Abs/[NaCl] data and compare pharmacological, toxicological, and pathological effects on the OF of RBC's.
Assuntos
Modelos Biológicos , Fragilidade Osmótica , Animais , Permeabilidade da Membrana Celular/fisiologia , Tamanho Celular , Membrana Eritrocítica , Feminino , Coelhos , Valores de Referência , Cloreto de Sódio/metabolismo , Organismos Livres de Patógenos Específicos , Espectrofotometria Ultravioleta , Estatística como AssuntoRESUMO
An in vitro study was conducted to determine whether indomethacin (IN) and oestradiol (E(2)) induced decreases in rabbit haematocrit may be related to their effect on erythrocyte fragility (EF). Aliquots of treated rabbit whole blood were assayed as control, IN (9.6 mug/ml), E(2) (500 pg/ml) and IN + E(2), for changes in EF. Osmotic (OF) and mechanical (MF) fragility in eight experimental replicates were evaluated under approximate physiological conditions by measurement of haemoglobin release. Samples were assayed immediately after drug addition and again 4 hr after incubation at 39.5 degrees C. OF results showed a significant increase in 50% haemolysis between final IN and IN + E(2) values when compared with their initial values and with controls. OF haemolysis dispersion was increased over time by IN and IN + E(2). MF increased with IN, E(2) and IN + E(2) versus their initial values and the controls. Although the increase in MF from IN was greater than that from E(2), the MF from IN + E(2) was not greater than that from IN alone. The IN induced increases in both OF and MF indicate a difference in degree of interaction with the erythrocyte from that of E(2), which affected only MF and the effect of which was neither additive nor synergistic with that of IN.
RESUMO
BACKGROUND AND PURPOSE: Pharmacokinetic assessment of drug tissue permeation following iontophoresis is limited. The depth of ketoprofen tissue permeation following cathodic iontophoresis (4 mA, 40 minutes) and the stereoselectivity of drug delivery were examined in this study. SUBJECTS: Ketoprofen (750 mg) was iontophoresed onto one porcine medial thigh, with passive drug permeation conducted on the other thigh. METHODS: Skin, subcutaneous fascia, and muscle biopsies from the drug delivery sites were harvested and stored separately, and the "R" and "S" ketoprofen enantiomers were determined. Results. Iontophoretic and passive applications yielded equivalent total ketoprofen concentrations in the skin and fascia. In contrast, multivariate analysis demonstrated that the ketoprofen concentration in the first centimeter of muscle following iontophoresis was greater than the drug concentration in the deeper underlying muscle layers and greater than that delivered to any muscle layer following passive delivery. No transcutaneous stereoselective delivery) of ketoprofen was detected. CONCLUSION AND DISCUSSION: Compared with passive delivery, iontophoresis enhances nonstereoselective ketoprofen permeation into the fascia-muscle interface. With delivery to deeper tissue sites, however, there is no apparent enhancement over passive application.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacocinética , Iontoforese/métodos , Cetoprofeno/administração & dosagem , Cetoprofeno/farmacocinética , Animais , Anti-Inflamatórios não Esteroides/análise , Cromatografia Líquida de Alta Pressão , Fáscia/química , Cetoprofeno/análise , Análise Multivariada , Músculos/química , Pele/química , Suínos , Distribuição TecidualRESUMO
A microanalytical method with direct on-column specimen injection for determination of 1,3-butylene glycol (1,3-butanediol) in whole blood or plasma using gas-liquid chromatography with flame ionization is described. Whole blood or serum (minimum of 10 microL) was mixed with an equal volume of internal standard (1,2-propanediol, 50 mg/dL) and a 2-microL aliquot was injected onto the column without prior derivatization or extraction. The other short chain (C2 to C4) alkyldiols were separated by this method and did not interfere with the quantitation of 1,3-butylene glycol. The method was linear (y = 0.0206x + [-0.0073], r = 0.9990) over the range of 25 to 100 mg/dL and the coefficient of variation varied between 0.74 and 6.03%. Minimum detectable concentration of 1,3-butylene glycol was 5.0 mg/dL. The method described is suitable for the rapid detection of potentially toxic blood or plasma levels of 1,3-butylene glycol, as well as for the detection of other short chain glycols.
Assuntos
Butileno Glicóis/sangue , Glicóis/isolamento & purificação , Animais , Cromatografia Gasosa , Glicóis/toxicidade , Humanos , Dose Letal Mediana , RatosRESUMO
2-Chloroacetophenone (CN) and o-chlorobenzylidene malononitrile (CS) are the most common chemical agents used as lacrimators in the United States. There is a lack of complete spectral data on these compounds in the literature. Spectral data (ultraviolet, fluorescence, proton nuclear magnetic resonance, and infrared) and a gas-liquid chromatographic/mass spectrometric method are presented that differentiate and identify CN and CS. These methods and data were used to identify a forensic science specimen from an accidental intoxication.
Assuntos
Cromatografia Gasosa-Espectrometria de Massas , Nitrilas/análise , Espectrofotometria , Gases Lacrimogênios/análise , o-Clorobenzilidenomalonitrila/análise , ômega-Cloroacetofenona/análise , Humanos , Gases Lacrimogênios/intoxicação , o-Clorobenzilidenomalonitrila/intoxicação , ômega-Cloroacetofenona/intoxicaçãoRESUMO
A case is presented of a fatal drug interaction caused by ingestion of methocarbamol (Robaxin) and ethanol. Methocarbamol is a carbamate derivative used as a muscle relaxant with sedative effects. Therapeutic concentrations of methocarbamol are reported to be 24 to 41 micrograms/mL. Biological fluids were screened for ethanol using the Abbott TDx system and quantitated by gas-liquid chromatography (GLC). Determination of methocarbamol concentrations in biological tissue homogenates and fluids were obtained by colorimetric analysis of diazotized methocarbamol. Blood ethanol concentration was 135 mg/dL (0.135% w/v) and urine ethanol was 249 mg/dL (0.249% w/v). Methocarbamol concentrations were: blood, 257 micrograms/mL; bile, 927 micrograms/L; urine, 255 micrograms/L; gastric, 3.7 g; liver, 459 micrograms/g; and kidney, 83 micrograms/g. The combination of ethanol and carbamates is contraindicated since acute alcohol intoxication combined with carbamate usage can lead to combined central nervous system depression as a result of the interactive sedative-hypnotic properties of the compounds.
Assuntos
Intoxicação Alcoólica , Metocarbamol/intoxicação , Adulto , Cromatografia Gasosa , Colorimetria , Interações Medicamentosas , Etanol/sangue , Humanos , Masculino , Metocarbamol/análiseRESUMO
A case is presented of a death caused by self-injection of sufentanil and midazolam. Biological fluids and tissues were analyzed for midazolam by high performance liquid chromatography (HPLC) and gas chromatography/mass spectrometry (GC/MS) and for sufentanil by GC/MS. Midazolam was extracted from basified fluids or tissues homogenated with n-butyl chloride and analyzed by HPLC by using a phosphate buffer: acetonitrile (60:40) mobile phase on a mu-Bondapak C18 column at 240 nm. Sufentanil was extracted from basified fluids and tissue homogenates with hexane:ethanol (19:1). GC/MS methodology for both compounds consisted of chromatographic separation on a 15-m by 0.25-mm inside diameter (ID) DB-5 (1.0-micron-thick film) bonded phase fused silica capillary column with helium carrier (29 cm/s) splitless injection at 260 degrees C; column 200 degrees C (0.8 min) 10 degrees C/min to 270 degrees C; and electron ionization and multiple ion detection for midazolam (m/z 310), methaqualone (IS, m/z 235), sufentanil (m/z 289), and fentanyl (IS, m/z 245). Sufentanil concentrations were: blood 1.1 ng/mL, urine 1.3 ng/mL, vitreous humor 1.2 ng/mL, liver 1.75 ng/g, and kidney 5.5 ng/g. Midazolam concentrations were: blood 50 ng/mL, urine 300 ng/mL, liver 930 ng/g, and kidney 290 ng/g. Cause of death was attributed to an acute sufentanil/midazolam intoxication and manner of death a suicide.
Assuntos
Fentanila/análogos & derivados , Midazolam/intoxicação , Suicídio/legislação & jurisprudência , Adulto , Fentanila/farmacocinética , Fentanila/intoxicação , Humanos , Injeções Intravenosas , Masculino , Midazolam/farmacocinética , Sufentanil , Distribuição TecidualRESUMO
A case is presented of a fatal ingestion of Furadan (carbofuran), a cholinesterase-inhibiting carbamate insecticide. A 26-year-old white male was found dead with a partially filled 1-gal (3.8-L) container of Furadan 4F insecticide-nematocide (44.9% carbofuran). The individual had ingested approximately 345 mL of the mixture. Analysis of cholinesterase activity in various biological fluids was performed spectrophotometrically using propionylthiocholine and 5,5'-dithiobis-2-nitrobenzoic acid [Sigma Diagnostics, cholinesterase procedure No. 422 (PTC)] which was measured at 405 nm and 30 degrees C in a Gilford Stasar III Spectrophotometer. The cholinesterase activities were as follows: plasma, 245 units (U)/L (93% inhibition/7% normal activity); serum, 208 U/L (95.3% inhibition/4.7% normal activity); whole blood, 297 U/L (92.8% inhibition/7.2% normal activity); erythrocytes, 58 U/L (99% inhibition/1% normal activity); vitreous humor, 7 U/L; and bile, 148 U/L. Carbofuran was detected in the blood and gastric contents by thin-layer chromatography. No alcohol or other drugs were detected in the blood, urine, or gastric contents. Ingestion of the carbofuran produced acute visceral congestion and pulmonary edema. Death was caused by anoxia due to respiratory paralysis produced by cholinesterase inhibition from Furadan (carbofuran) ingestion.
Assuntos
Carbofurano/intoxicação , Colinesterases/análise , Adulto , Carbofurano/análise , Carbofurano/sangue , Inibidores da Colinesterase/análise , Cromatografia Gasosa , Cromatografia em Camada Fina , Overdose de Drogas , Conteúdo Gastrointestinal/química , Humanos , Hipóxia/induzido quimicamente , Masculino , SuicídioRESUMO
Pursuant to a recent driving under the influence (DUI) case, a medical study of six subjects was cited reporting that ibuprofen causes a decrease in the maximum rate of elimination of ethanol. Such a drug interaction is of significant forensic science interest and warrants further examination. This study investigates the effect of ibuprofen on ethanol elimination rate and ethanol concentration in nineteen volunteers. Volunteer subjects were randomly assigned to two groups administered either a placebo followed by ethanol or ibuprofen followed by ethanol. Subjects served as their own control. Blood ethanol concentrations were monitored every 30 to 60 min for up to 4 h with Intoximeter 3000 instruments. A blood sample was drawn at the final Intoximeter test and analyzed for ethanol and ibuprofen by gas chromatography and mass spectrometry, respectively. The mean elimination rate (+/- SD) as calculated using Widmark's elimination factor was 0.018 +/- 0.006 g/dL for ethanol and 0.017 +/- 0.007 g/dL/h for ethanol with ibuprofen. Mean ethanol concentrations (g/dL +/- SD) were: 0.095 +/- 0.026 (ethanol) and 0.095 +/- 0.033 (ethanol and ibuprofen) at 30 min; 0.077 +/- 0.026 (ethanol) and 0.075 +/- 0.031 (ethanol and ibuprofen) at 150 min; and 0.089 +/- 0.025 (ethanol) and 0.087 +/- 0.030 (ethanol and ibuprofen) overall. There was no statistically significant affect of ibuprofen on either the peak blood ethanol concentration or the ethanol elimination rate (p less than or equal to 0.001). These results reveal no evidence of a significant ethanol-ibuprofen interaction.
Assuntos
Etanol/farmacocinética , Ibuprofeno/farmacologia , Cromatografia Gasosa , Interações Medicamentosas , Etanol/sangue , Feminino , Humanos , Masculino , Distribuição AleatóriaRESUMO
Normal human urine contains many anions and cations. Ionic concentrations in urine have classically been determined by spectrophotometry of color reactions, flame emission spectrophotometry, atomic absorption spectrophotometry, high performance liquid chromatography, or potentiometry with ion-specific electrodes. Capillary ion electrophoresis (CIE) is a form of capillary electrophoresis which uses the differential electrophoretic mobility of ions to perform a separation of an ionic mixture. Various salts can be added to urine specimens to abnormally elevate ionic concentrations and interfere with either immunoassay urine drug screening procedures or gas chromatographic/mass spectrometric confirmation techniques. Application of CIE for the direct detection of endogenous anions and anionic adulterants in human urine specimens was the purpose of this investigation. CIE was performed using a Waters Quanta 4000 Capillary Electrophoresis System with either direct or indirect ultraviolet absorption detection at 254 nm. CIE of 30 random normal urine specimens and 21 urine specimens suspected of adulteration was performed. Duplicate aliquots were assayed by CIE and by colorimetric technique for nitrite. Sixteen specimens had elevated concentrations of nitrite and/or nitrate. The correlation coefficient between nitrite CIE and colorimetric results was 0.9895. Three specimens had detectable concentrations of chromate and were suspected of being adulterated with "Urine Luck," an adulterant found to contain chromate. Two specimens suspected of being adulterated with bleach were found to only contain chloride, sulfate, and phosphate. CIE is applicable to forensic analysis of urine anion concentrations. CIE can easily quantitate numerous endogenous anions and offers a method to detect and/or confirm anion adulteration of urine specimens.
Assuntos
Ânions/urina , Contaminação de Medicamentos , Eletroforese Capilar/métodos , Detecção do Abuso de Substâncias/métodos , Adulto , Humanos , Sensibilidade e EspecificidadeRESUMO
Micellar electrokinetic capillary chromatography (MECC) is a form of capillary zone electrophoresis. Addition of a surfactant produces micelles in an aqueous/organic buffer. Separation of drugs is obtained via differences in the electrophoretic mobilities of the analytes within the capillary, resulting from their electrophoretic velocity and the electroosmotic flow of the buffer in a given electric field. The migration order is determined by the differential partitioning of the drugs between the micelles and the aqueous/organic phase. Barbiturates were extracted from various biological fluids at pH 4.5 with TOXI-TUBES B. MECC analyses were performed using a Waters Quanta 4000 Capillary Electrophoretic System with a 745 Data Module with a 75 microns x 60 cm capillary and an aqueous/organic buffer of 85% 10 mM borate, 10 mM phosphate, 100 mM sodium dodecyl sulfate and 15% acetonitrile at a pH of 8.5 with a voltage of 20 kV using ultraviolet absorption detection at 214 nm. Migration times were: phenobarbital, 7.78 min.; butalbital, 8.01 min.; butabarbital, 8.23 min.; mephobarbital (internal standard), 8.88 min.; amobarbital, 9.41 min.; pentobarbital, 10.03 min. and secobarbital, 10.79 min. Correlation coefficients (r) between peak areas and concentration ranges of 3 to 60 micrograms/mL were from 0.964 to 0.999. Coefficients of variation (CV) ranged from 2.6 to 8.6% between days and 2.3 to 9.8% within day. Application of this methodology to four forensic cases of butalbital intoxication detected concentrations of 0.7 to 12.7 micrograms/mL in blood; 0.8 to 1.9 micrograms/mL in vitreous humor and 1.5 to 7.6 micrograms/mL in urine. MECC is applicable to forensic analysis of barbiturates extracted from biological fluids.
Assuntos
Barbitúricos/análise , Líquidos Corporais/química , Eletroforese/métodos , Medicina Legal/métodos , Medicina Legal/instrumentação , Humanos , Análise de Regressão , Reprodutibilidade dos Testes , Manejo de EspécimesRESUMO
A case is presented of a fatal drug interaction caused by ingestion of clozapine (Clozaril) and fluoxetine (Prozac). Clozapine is a tricyclic dibenzodiazepine derivative used as an "atypical antipsychotic" in the treatment of severe paranoid schizophrenia. Fluoxetine is a selective serotonin reuptake inhibitor used for the treatment of major depression. Clinical studies have proven that concomitant administration of fluoxetine and clozapine produces increased plasma concentrations of clozapine and enhances clozapine's pharmacological effects due to suspected inhibition of clozapine metabolism by fluoxetine. Blood, gastric, and urine specimens were analyzed for fluoxetine by gas chromatography/mass spectrometry (GC/MS) and for clozapine by gas-liquid chromatography (GLC). Clozapine concentrations were: plasma, 4.9 micrograms/mL; gastric contents, 265 mg; and urine, 51.5 micrograms/mL. Fluoxetine concentrations were: blood, 0.7 microgram/mL; gastric contents, 3.7 mg; and urine 1.6 micrograms/mL. Norfluoxetine concentrations were: blood, 0.6 microgram/mL, and none detected in the gastric contents or urine. Analysis of the biological specimens for other drugs revealed the presence of ethanol (blood, 35 mg/dL; vitreous, 56 mg/dL; and urine 153 mg/dL) and caffeine (present in all specimens). The combination of these drugs produced lethal concentrations of clozapine and high therapeutic to toxic concentrations of fluoxetine. The deceased had pulmonary edema, visceral vascular congestion, paralytic ileus, gastroenteritis and eosinophilia. These conditions are associated with clozapine toxicity. The combined central nervous system, respiratory and cardiovascular depression of these drugs was sufficient to cause death. The death was determined to be a clozapine overdose due to a fatal drug interaction.
Assuntos
Antipsicóticos/intoxicação , Clozapina/intoxicação , Fluoxetina/intoxicação , Inibidores Seletivos de Recaptação de Serotonina/intoxicação , Antipsicóticos/farmacocinética , Clozapina/farmacocinética , Interações Medicamentosas , Overdose de Drogas , Evolução Fatal , Fluoxetina/farmacocinética , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores Seletivos de Recaptação de Serotonina/farmacocinéticaRESUMO
The Pursuit Meter II, a microcomputer-based device developed for the quantitative determination of human pursuit-tracking performance, is described. Computer-generated moving patterns are displayed on a high resolution color video monitor. For the subject the task is to attempt to superimpose a red line presented on the screen, the vertical location of which he controls with a steering device, over a blue line the computer generates as the problem. Both lines, each composed of 279 segments, are generated at the same rate, left to right on the monitor. The individual differences between the subject's response and the problem are summed and stored by the computer as an error score which correlates inversely to the subject's ability to perform the task. Three Pursuit Meter II problems were presented to 26 male college students. Our data demonstrated that different levels of performance to the problems resulted and that the Pursuit Meter II can be used to quantify human pursuit-tracking performance.
Assuntos
Computadores , Microcomputadores , Percepção de Movimento , Destreza Motora , Psicologia/instrumentação , Aprendizagem por Discriminação , Humanos , MasculinoAssuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Carpo Animal/metabolismo , Cavalos/metabolismo , Cetoprofeno/administração & dosagem , Animais , Anti-Inflamatórios não Esteroides/análise , Anti-Inflamatórios não Esteroides/farmacocinética , Cromatografia Líquida de Alta Pressão , Feminino , Iontoforese/veterinária , Cetoprofeno/análise , Cetoprofeno/farmacocinética , Coxeadura Animal/tratamento farmacológico , Membrana Sinovial/metabolismoAssuntos
Ácido Arsanílico/farmacologia , Arsênio/análise , Arsenicais/farmacologia , Suínos/metabolismo , Fosfatase Alcalina/sangue , Animais , Ácido Arsanílico/metabolismo , Nitrogênio da Ureia Sanguínea , Peso Corporal , Fezes/análise , Rim/análise , Fígado/análise , Músculos/análise , Suínos/sangue , Suínos/crescimento & desenvolvimento , gama-Glutamiltransferase/sangueRESUMO
Ethylene glycol (EG) is a toxic chemical found in antifreeze and heat exchangers. Standard therapy for EG intoxication in administration of ethanol (ETOH) to inhibit its metabolism by alcohol dehydrogenase (ADH). Studies indicate 1,3-butylene glycol (BG) binds to ADH more efficiently than EG and is orally less toxic than EG or ETOH. Male rats were divided into 5 groups of 6 animals. Groups received by oral intubation a single dose of EG (32 mmole/kg), BG (39 mmole/kg) initially and every 6 h up to 72 h, ETOH (39 mmole/kg) initially and every 6 h up to 72 h, or EG initially and then either BG or ETOH every 6 h up to 72 h. Administration of ETOH produced hepatotoxicity and pulmonary pathology as indicated by changes in clinical chemistry, urinalysis, and histopathology, while BG did not. Neither ETOH nor BG produced any apparent nephrotoxicity. ETOH produced ataxia, lethargy and central nervous system depression while BG did not. BG produced a higher concentration of urinary EG indicating a better inhibition of ADH metabolism of EG. Ethanol produced a higher EG blood concentration than BG. Ethanol's higher EG blood concentration may be partially attributed to dehydration and a decreased urine output as well as inhibition of ADH metabolism. Ethanol produced mortality in all animals prior to 72 h. The EG/ETOH combination produced mortality more quickly due to additive toxicity of the combination. Lack of any significant toxicity produced by BG and the production of significant toxicities by ETOH indicates that BG is potentially a better antidote than ETOH.