RESUMEN
PURPOSE: This study aimed to conduct a diagnostic and cost-effective analysis of the cytopathology assistance in the ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) for characterising thyroid nodules. MATERIALS AND METHODS: We reviewed the reports relative to 9061 US-guided FNABs for the histologic definition of the nature of thyroid nodules: 45.4% completed with the cytopathologist assistance and 54.6% by the radiologist alone. We also performed the cost-effectiveness analysis (CEA) of the procedure with and without the cytopathologist assistance. RESULTS: We found a significant positive correlation between the adoption/non-adoption of cytopathologist assistance and the number of indeterminate (TIR1) (Chi-square; z-score, Z = 10.22; critical value 5%, C = 1.96; p < 0.001). The cytopathologist's absence was correlated with the number of TIR 1 (Pearson correlation, product-moment correlation r = 0.059; critical value 5%, C = 0.008; p < 0.001). The total cost of the model's cytopathologist-assistance branch is 109.87, while the total cost of the non-cytopathologist-assistance branch is 95.08. CONCLUSION: The cytopathologist assistance resulted in fewer nondiagnostic results, thus excluding the procedure's repetition but involved a higher expense, mainly due to the professional cost of the pathologist's participation. These data may provide decision-makers in healthcare with a practical evidence based on the opportunity to include the cytopathologist assistance in the thyroid nodule's FNAB depending on the available resources and the population's expectance.
RESUMEN
BACKGROUND: The purpose of this descriptive, epidemiological study is to classify injury patterns and determine dynamics of injuries, possible causes and preventive measures. METHODS: A questionnaire was filled in by 127 kite buggying enthusiasts in 17 countries. Injuries were classified by type and anatomical site. Incident causes were analysed using the Haddon matrix. RESULTS: Injuries classified as moderate or severe (AIS score ≥ 2) were sustained by 26% of kite buggy enthusiasts. The most common incident dynamic (61.8%) was the OBE (an acronym for 'out-of-buggy experience'). Causal factors were largely equipment-related (42.3%), with remaining incidents being equally attributable to environmental and human factors. While upper and lower limbs were equally involved in incidents, the most frequently affected anatomical site was the shoulder (23%). CONCLUSION: Kite buggying can be considered a sport with the potential for serious injury. Injury prevention in this sport needs to be approached from several angles and should include the development and adoption of automatic release systems and shoulder guards, the establishment of formal training programs covering the subject of meteorology and the establishment of secure, designated kite buggying areas. Findings from this study are important for two reasons. First, they demonstrate the significance of understanding specific sports when considering health and safety, and second, the study provides specific data for the fast growing extreme sport of kite buggying.
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Traumatismos en Atletas/epidemiología , Traumatismos en Atletas/prevención & control , Ropa de Protección/estadística & datos numéricos , Asunción de Riesgos , Deportes/psicología , Encuestas y Cuestionarios , Adulto , Traumatismos en Atletas/psicología , Femenino , Humanos , Internacionalidad , Masculino , Persona de Mediana EdadRESUMEN
The aim of this study was to evaluate the possible effects of nicergoline, a semisynthetic ergot derivative, on the biochemical changes observed during chronic treatment with haloperidol in male Sprague-Dawley rats. Chronic treatment with haloperidol induced a significant decrease in the cellular glutathione (GSH) content in selected areas of the brain (cerebellum, striatum and cortex) and in the liver. Prolonged nicergoline administration was able to antagonize the haloperidol-induced GSH decrease, maintaining the GSH concentration at levels comparable to those observed in the control group. Analysis of the energy charge revealed changes similar to those observed for GSH: haloperidol induced a significant decrease in ATP and energy charge that was completely reversed by repeated nicergoline administration. In conclusion, chronic treatment with the classical antipsychotic haloperidol induces profound biochemical changes in the brain and in the liver. Nicergoline treatment is able to counteract the haloperidol-induced decrease in GSH levels and energy charge, suggesting a potential role of the drug in the treatment of neuroleptic-induced side effects.
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Antipsicóticos/farmacología , Metabolismo Energético/efectos de los fármacos , Glutatión/efectos de los fármacos , Haloperidol/farmacología , Adenosina Trifosfato/metabolismo , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Cerebelo/efectos de los fármacos , Cerebelo/metabolismo , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Glutatión/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Neostriado/efectos de los fármacos , Neostriado/metabolismo , Nicergolina/farmacología , Ratas , Ratas Sprague-Dawley , Vasodilatadores/farmacologíaRESUMEN
The antiproteasic activity of alpha1-antitrypsin (alpha1-AT) is reduced in cases of subarachnoid hemorrhage from ruptured intracranial aneurysm and particularly in patients currently smoking; alpha1-AT is very sensitive to oxidant agents. About 50% of physiological anti-oxidant systemic capacity is represented by Vitamin A, E and C. Plasmatic amounts of alpha1-AT, alpha1-AT Collagenase Inhibitory Capacity (CIC) and levels of vitamin A, vitamin E and vitamin C were analyzed in 39 patients, 26 women and 13 men, operated for intracranial aneurysm; 11 patients with unruptured intracranial aneurysm were considered as controls while 28 patients were included within 12 hours from subarachnoid hemorrhage (SAH). Plasmatic levels of vitamin A and vitamin E were significantly lower (p=0.038 and p=0.0158) in patients suffering SAH than in controls, while no statistically significant differences were found in mean plasmatic vitamin C levels. Level of alpha1-AT was not statistically different in controls and in patients with SAH; however, the activity of alpha1-AT, evaluated as CIC, is significantly reduced in patients with SAH (p=0.019). We have observed that systemic plasmatic levels of vitamins did not significantly differ in relation to smoking habit. Vitamin A and E represent an important defensive system against free radicals reactions. Particularly, vitamin E acts as an antioxidant by scavenging free-radicals. A reduced anti-oxidant status might be related to the higher sensibility of alpha1-AT to oxidative reactions and the activity of alpha1-AT is dependent on the antioxidant capacity of liposoluble vitamins. We can speculate that an acute systemic oxidative stress condition might influence the rupture of intracranial aneurysms.
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Antioxidantes/metabolismo , Hemorragia Subaracnoidea/metabolismo , alfa 1-Antitripsina/metabolismo , Ácido Ascórbico/sangre , Femenino , Humanos , Aneurisma Intracraneal/metabolismo , Masculino , Persona de Mediana Edad , Estrés Oxidativo/fisiología , Fumar/sangre , Hemorragia Subaracnoidea/enzimología , Vitamina A/sangre , Vitamina E/sangreRESUMEN
Prolonged medication with diltiazem has proved advantageous in the treatment of coronary insufficiency and arterial hypertension. Consistently, a number of extended release formulations, based on different retardation mechanisms, have been proposed. In the present work two prolonged release oral formulations containing diltiazem, one intended for twice-a-day and one for once-a-day administration, were tested for in vitro behaviour; the in vitro release test had been opportunely validated using an in vitro-in vivo correlation approach. On the basis of in vitro release profiles, simulations were effected, using a computer program previously developed, in order to generate the plasma levels that could be expected on single dosing of the two formulations. The two formulations were then tested in vivo and the measured plasma profiles were compared with those predicted from in vitro data. For both formulations, a good agreement was found between the measured and the simulated plasma levels, thus demonstrating the usefulness of the simulation approach in the formulative development.
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Simulación por Computador , Preparaciones de Acción Retardada , Adulto , Diltiazem/administración & dosificación , Diltiazem/química , Diltiazem/farmacocinética , HumanosRESUMEN
A preliminary in-vivo study was performed on a new modified release system which contained diltiazem hydrochloride. The system consisted of swellable minimatrices that were coated with an acrylic polymeric film. The film thickness, because of its pH-dependent solubility, might represent a critical variable with regard to in-vivo release. In order to evaluate the influence of such a variable on in-vivo behaviour, two minimatrices formulations with differing film thickness were tested versus a commercial tablet. The in-vivo study, which was based on a balanced incomplete block design, involved six volunteers in two sequences. The drug was quantified in plasma by an HPLC method. Computation and statistical analysis of pharmacokinetic parameters were performed by means of SIPHARR package (Simed, F). The results show that the approach of film coating, in order to modify the release rate from minimatrices, is feasible, but it must be improved; in particular the results point to the necessity of reducing the film susceptibility to pH changes.
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Preparaciones de Acción Retardada , Adulto , Química Farmacéutica , Cromatografía Líquida de Alta Presión , Excipientes , HumanosRESUMEN
In a cross-over study performed on 10 patients the intranasal absorption of calcitonin contained in three formulation spray was evaluated. One of them contained biliary acid (sodium taurocholate) as the absorption promoting factor while the other two drugs did not. The dosage of calcitonin in blood was effected by means of radioimmunoassay using salmon calcitonin marked with I126 in competition to the one present in the sample for a limited quantity of specific antibodies for salmon calcitonin. The minimum measurable quantity of calcitonin is 10 pg and the response is linear including values between 20% and 80%. It is observed that the plasmatic concentration of calcitonin dosed in different times after administration of the drug containing sodium taurocholate are always significantly higher (Student "t" test for unpaired data, p less than 0.005) than the measurements after administration of the other two drugs. They are about 8 times higher at the first half an hour, about 6 times after an hour and again double at the second hour. The AUC calculated for sodium taurocholate containing drug (1629 pg/ml/h) results significantly higher in relation to the other two drugs (1133 and 926 pg/ml/h) indicating a better bio-availability of calcitonin contained in that spray. The relative bioavailability between calcitonin spray with sodium taurocholate and the other two drugs in reference resulted to 144% and 176%. The presence of a transmucosal absorption promoting factor at the level of a nasal mucosa, represented in this case by sodium taurocholate, enhances significantly the absorption and the bioavailability of calcitonin present in the formulation spray.
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Calcitonina/farmacocinética , Administración Intranasal , Adulto , Calcitonina/administración & dosificación , Femenino , Humanos , MasculinoRESUMEN
PURPOSE: The aim of this study was to evaluate the usefulness of imaging for correct clinical and therapeutic management of patients with scrotal disease. MATERIALS AND METHODS: Between 2000 and 2007, 801 patients with suspected scrotal disease underwent colour Doppler ultrasonography (CDUS) at our centre. In 46 patients, the CDUS study was followed by magnetic resonance imaging (MRI). RESULTS: CDUS revealed an inflammatory process in 277 patients (34.58%), testicular trauma in 112 (13.9%), funicular torsion or torsion of the vestigial remnant in 44 (5.4%), findings suggestive of testicular neoplasm in 35 (4.3%) and no abnormality in 41.5%. MRI, used to further investigate the CDUS findings in 46 cases, showed three cases of intraparenchymal haematoma, one of intrascrotal cavernous body rupture, one of testicular abscess with intrascrotal fistula, two of testicular infarction and 15 of neoplasm. MRI allowed the exclusion of focal abnormalities in ten patients with testicular microlithiasis, in three with chronic orchitis and in four with atrophic involution. MRI confirmed the finding of inguinal hernia in three cases. CONCLUSIONS: On the basis of our experience, CDUS is irreplaceable as an initial approach to patients affected by scrotal disease, whereas MRI is an ideal second-line investigation. MRI offers useful, and in some cases decisive, information, as it is capable of revealing unexpected findings and elucidating complex aspects. MRI helps improve patient management, with an overall reduction in costs.
Asunto(s)
Imagen por Resonancia Magnética , Escroto/anatomía & histología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Enfermedades de los Genitales Masculinos/diagnóstico , Hernia Inguinal/diagnóstico , Humanos , Lactante , Recién Nacido , Inflamación/diagnóstico , Masculino , Persona de Mediana Edad , Escroto/diagnóstico por imagen , Neoplasias Testiculares/diagnóstico , Testículo/lesiones , Anomalía Torsional/diagnóstico , Ultrasonografía Doppler en ColorRESUMEN
Diltiazem was able to decrease the oxygen consumption rate and lactate production in synaptosomes isolated from rat forebrains, both under control and depolarized (40 microM veratridine) conditions, starting from a concentration of 250 microM. This effect was particularly evident when synaptosomes were depolarized by veratridine. This depolarization-counteracting action was evident also when transplasma membrane K+ diffusion potentials were measured after depolarization induced by veratridine and by rotenone with a glucose shortage. The concentrations of ATP, phosphocreatine, and creatine were less sensitive to diltiazem action. The concentration/response relationships were the same as those found for the oxygen consumption were the same as those found for the oxygen consumption rate, lactate production, and K+ diffusion potentials. The effects of 0.5 mM diltiazem in counteracting inhibition of energy metabolism induced by rotenone without glucose were no longer detectable when either Ca2+ or Na+ was absent from the incubation medium of synaptosomes. Diltiazem at the same concentrations (starting from 250 microM) was able to inhibit both the veratridine-induced and the rotenone-without-glucose-induced increase in intrasynaptosomal free Ca2+ levels evaluated with the fluorescent probe quin2. The results are discussed in view of a possible effect of diltiazem on voltage-dependent Na+ channels and the possibility of utilizing this approach for counteracting neuronal failure due to derangement of energy metabolism or hyperexcitation.
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Encéfalo/metabolismo , Calcio/metabolismo , Diltiazem/farmacología , Metabolismo Energético/efectos de los fármacos , Potasio/fisiología , Sinaptosomas/metabolismo , Animales , Encéfalo/fisiología , Encéfalo/ultraestructura , Calcio/deficiencia , Citosol/metabolismo , Relación Dosis-Respuesta a Droga , Electrofisiología , Concentración Osmolar , Ratas , Rotenona/farmacología , Sodio/deficiencia , Sinaptosomas/fisiología , Sinaptosomas/ultraestructura , Veratridina/farmacologíaRESUMEN
The reproductive toxicity of taurohyodeoxycholic acid (3 alpha, 6 alpha-dihydroxy-5-beta-cholanoyl-2-amino-ethyl-sulfonic acid, THDCA, Io, Praxis, CAS 2958-04-5), a new synthetized biliary acid patented in Europe, Japan and the United States for prevention and therapy of gallstones and related symptoms, was assayed by performing segment I (fertility and general reproductive performance) and segment II (teratology) studies. In the first study THDCA was administered (100, 220 or 500 mg/kg by oral route) to male and female rats prior to and in the early stage of pregnancy. No adverse effects or dose-related abnormalities were observed in the reproductive performance of either sex; no death or evidence of teratogenicity in fetuses were also observed. In the second study THDCA was administered (100, 220 or 500 mg/kg by oral route) to rats and rabbits during the fetal organogenesis period. No maternal toxicity, teratogenicity or adverse effects on growth of embryos and fetuses and no reduction of the viability index were observed. From these studies the no-effect dose can be estimated at 500 mg/kg.
Asunto(s)
Colagogos y Coleréticos/toxicidad , Fertilidad/efectos de los fármacos , Reproducción/efectos de los fármacos , Ácido Taurodesoxicólico/análogos & derivados , Teratógenos/toxicidad , Anomalías Inducidas por Medicamentos/patología , Animales , Peso al Nacer/efectos de los fármacos , Implantación del Embrión/efectos de los fármacos , Femenino , Muerte Fetal/inducido químicamente , Reabsorción del Feto/inducido químicamente , Masculino , Embarazo , Conejos , Ratas , Ratas Sprague-Dawley , Razón de Masculinidad , Ácido Taurodesoxicólico/toxicidadRESUMEN
The mutagenicity of a new biliary acid, taurohyodeoxycholic acid (THDCA, Io, Praxis, CAS 2958-04-5), was assayed by using 5 different tests. The Ames test (reverse mutation assay on Salmonella typhimurium) and the DNA damage and repair test (in Saccharomyces cerevisiae) allowed to study the genetic THDCA-induced mutations in prokaryotes and eukaryotes (doses of 100, 200 and 400 micrograms/plate or 100, 200 and 400 micrograms/ml, respectively). In vivo and in vitro chromosomal aberrations were studied by using micronucleus test in mice (doses of 100, 220 and 500 mg/kg in oral study and 50, 100 and 200 mg/kg in subcutaneous study) and human lymphocytes cytogenetic test (doses of 50, 100, 220 and 500 micrograms/ml of THDCA). At last the host-mediated assay was performed on THDCA-treated mice (following oral or subcutaneous administration) in order to test the potential mutagenic activity of its metabolites on a S. typhimurium strain. The results obtained in these studies showed that THDCA did not induce any signs of promutagenic, mutagenic or clastogenic direct or metabolite-mediated activity.
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Colagogos y Coleréticos/toxicidad , Mutágenos/toxicidad , Ácido Taurodesoxicólico/análogos & derivados , Adulto , Animales , Aberraciones Cromosómicas , Intercambio Genético/efectos de los fármacos , Medios de Cultivo , Daño del ADN , Reparación del ADN , Femenino , Conversión Génica/efectos de los fármacos , Humanos , Técnicas In Vitro , Linfocitos/ultraestructura , Masculino , Ratones , Pruebas de Micronúcleos , Persona de Mediana Edad , Mitosis/efectos de los fármacos , Pruebas de Mutagenicidad , Ratas , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/genética , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genética , Ácido Taurodesoxicólico/toxicidadRESUMEN
We explored the bioavailability and kinetics of naproxen (N) in 12 healthy volunteers treated orally with single doses of 500 mg and retreated after a washout period with the same dose of N plus sulglycotide (S) 200 mg. Naproxen blood levels were measured by high-performance liquid chromatography (HPLC) in samples collected at 0.5, 1, 2, 4, 8, 12, and 24 h of dosing with N or with N + S. No statistically significant difference in terms of naproxen blood levels emerged as the product was administered alone or concurrently with sulglycotide. Peak plasma concentrations and AUC values were 71 +/- 3.16 micrograms/ml and 685 +/- 27 micrograms/ml/h, respectively for N alone, and 72.5 +/- 2.85 micrograms/ml and 651 +/- 28 micrograms/ml/h, respectively for N + S. The difference was not significant. Similarly, the kinetic behavior of naproxen was not modified by the simultaneous presence of sulglycotide, as shown by the t1/2 beta-values obtained with N alone (8.39 +/- 0.31 h) and with N + S (7.93 +/- 0.30 h), and likewise by the distribution volumes at equilibrium (7.63 +/- 0.42 and 7.9 +/- 0.38, respectively), Cmax (63.3 +/- 2.86 and 60.4 +/- 2.9 micrograms/ml, respectively) and tmax (0.95 +/- 0.06 and 1.10 +/- 0.10 h, respectively). From these findings it seems legitimate to claim that sulglycotide can be administered concurrently with naproxen to prevent possible gastric injury by the anti-inflammatory agent thanks to its wellknown antiulcer and cytoprotective activity on the gastric mucosa, without any undue interference with the absorption (hence effectiveness) of naproxen.
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Antiulcerosos/farmacología , Naproxeno/farmacocinética , Sialoglicoproteínas/farmacología , Adulto , Disponibilidad Biológica , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Masculino , Valores de ReferenciaRESUMEN
The pharmacokinetic pattern of erythromycin propionate-N-acetylcysteinate (EPAC) (erythromycin stinoprate I.N.N.), a new derivative, was studied on 12 healthy volunteers after single and multiple oral treatments. Microbiological and/or HPLC analytical methods were used to titer either erythromycin as base, propionate and total or N-acetylcysteine (NAC). In the acute experiment, a comparative evaluation was performed with erythromycin stearate (ES) and with N-acetylcysteine, according to a randomized-multi-crossover design. EPAC showed a better bioavailability than ES with longer-lasting serum levels of active antibiotic. NAC concentrations in the serum after EPAC were practically identical to those found after an oral administration of NAC alone. The multiple treatment study, performed in the same 12 volunteers with only EPAC, indicated that the pharmacokinetic pattern is somewhat different from that observed after a single dose, since higher concentrations were present at the steady state conditions.
Asunto(s)
Acetilcisteína/análogos & derivados , Acetilcisteína/farmacocinética , Eritromicina/análogos & derivados , Acetilcisteína/sangre , Adulto , Disponibilidad Biológica , Eritromicina/sangre , Eritromicina/farmacocinética , Femenino , Semivida , Humanos , Masculino , Tasa de Depuración Metabólica , Persona de Mediana EdadRESUMEN
Fifty-two-week oral toxicity and 24-week intramuscular toxicity of a new synthetized biliary acid, taurohyodeoxycholic acid (Io, Praxis, CAS 2958-04-5) were investigated in dogs. Taurohyodeoxycholic acid was orally administered at dose levels up to 500 mg/kg/d and i.m. administered at dose levels up to 200 mg/kg/d. No deviations from normality were observed in mortality, physical appearance and general behaviour of the treated animals. Food and water consumption and body weight gain of treated groups did not differ from those of control animals. No treatment-related changes were observed in hematology, serum biochemistry, urinalysis, organ weights and post-mortem macroscopic or histopathological examinations. No dose- or sex-related differences were observed. The no-effect dose level was estimated to be 500 mg/kg/d in the chronic oral toxicity study and 200 mg/kg/d in the intramuscular study.
Asunto(s)
Colagogos y Coleréticos/toxicidad , Ácido Taurodesoxicólico/análogos & derivados , Administración Oral , Animales , Análisis Químico de la Sangre , Peso Corporal/efectos de los fármacos , Colagogos y Coleréticos/sangre , Colagogos y Coleréticos/orina , Perros , Ingestión de Líquidos/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Femenino , Inyecciones Intramusculares , Masculino , Tamaño de los Órganos/efectos de los fármacos , Ácido Taurodesoxicólico/sangre , Ácido Taurodesoxicólico/toxicidad , Ácido Taurodesoxicólico/orinaRESUMEN
Fifty-two-week oral toxicity of a new glucan (Glucanil, Gluimmun) extracted from Candida albicans ATCC 20955 was investigated in rats. The glucan was orally administered in dose levels up to 200 mg/kg/d and was well tolerated. No deviation from normality was observed in mortality, physical appearance and general behaviour of the treated animals. Food and water consumption and body weight gain of glucan-fed groups did not differ from those of control animals. In these groups no alteration of the weight of the main organs was also observed. Hematology, blood chemistry, urinalysis and autopsy findings were within normal ranges in every group of rats treated. No sex difference was noted. In the 200 mg/kg group soft stools or diarrhoea and cecal enlargement with variable hyperplasia of the colon mucosa were observed. These symptoms are typical of exposure to substances which are absorbed incompletely in the small intestine and subjected to microbial metabolism in the cecum and colon. Diarrhoea, cecal enlargement and mucosal hyperplasia are reversible. The no-effect dose level was estimated to be 100 mg/kg/d under these conditions.
Asunto(s)
Candida albicans/metabolismo , Glucanos/toxicidad , Animales , Recuento de Células Sanguíneas , Análisis Químico de la Sangre , Peso Corporal/efectos de los fármacos , Candida albicans/química , Ingestión de Líquidos/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Femenino , Glucanos/aislamiento & purificación , Masculino , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Sprague-DawleyRESUMEN
The pharmacokinetics of a sustained release (SR) formulation of pyridoxal phosphate of buflomedil (Pirxane retard) has been studied after oral administration to healthy volunteers using among else a gaschromatographic dosage method. After oral administration of 400 mg of the SR formulation, pyridoxal phosphate of buflomedil has a much slower kinetics compared to the normal formulation (tmax:approx. 1.5 h) reaching the maximum plasma concentration, which was about 467 ng/ml, in about 3 h. After 24 h the concentrations were still about 1/10 (48 ng/ml) the maximum value. 24-h urinary excretion was about 21% of the administered dose. Repeated administration of the SR formulation for 7 days in single daily doses of 400 mg gave steady state plasma levels (ca. 250 ng/ml) 12 h after the administration without statistically significant variations. The plasma concentrations of the drug measured daily after reaching the steady state were similar one to the other. The tolerability was very good and no local or systemic side effects of any kind were reported.
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Fosfato de Piridoxal/farmacocinética , Pirrolidinas/farmacocinética , Adulto , Cromatografía de Gases , Preparaciones de Acción Retardada , Excipientes , Femenino , Humanos , Indicadores y Reactivos , Masculino , Fosfato de Piridoxal/administración & dosificación , Pirrolidinas/administración & dosificaciónRESUMEN
The pharmacokinetics and bioavailability of suckable tablets and granules of N-acetylcysteine (NAC) have been compared after oral administration of 400 mg doses to 10 healthy volunteers. The oral bioavailability of the NAC tablets was 103%. In a multiple dosing study of the same tablets in the same subjects, a high maintenance plasma level of NAC was revealed.
Asunto(s)
Acetilcisteína/farmacocinética , Acetilcisteína/administración & dosificación , Administración Oral , Adulto , Disponibilidad Biológica , Composición de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , ComprimidosRESUMEN
The pharmacokinetic properties of a new gastroprotective pharmaceutical formulation of diclofenac (CAS 15307-79-6) were investigated in twelve healthy volunteers. In this new form the diclofenac is the nucleus of sequential sucralfate-covered tablets. The experimental design was an open, random, two period balanced cross-over study. All the subjects received a single oral dose of 50 mg diclofenac contained in the new formulation or in the reference enteric-coated tablets. Plasma concentrations of diclofenac were determined at 0.5, 1, 2, 4, 6, and 8 h after drug administration using HPLC method. After administration of a diclofenac-sucralfate association diclofenac was quickly absorbed and the peak plasma concentration (0.773 +/- 0.08 microgram/ml) was achieved in about 1 h. AUC(0-infinity) value was about 1.8 micrograms/ml/h and the mean elimination half-life was 1.20 +/- 0.12 h. The pharmacokinetic profile of diclofenac-sucralfate association is similar to the values reported in previous papers for enteric-coated forms; anyway an early occurrence of the peak plasma concentration was observed for the new formulation. The new diclofenac-sucralfate association shows a different rate of absorption (namely an early and greater peak plasma concentration of diclofenac) and a similar extent of absorption (AUC(0-infinity) being not statistically different) as compared to the reference enteric-coated tablets of 50 mg diclofenac. These results could be related to the delaying and protective effect of sucralfate whose action is different from the one carried by the coat of the enteric-coated tablets.
Asunto(s)
Antiulcerosos/farmacocinética , Diclofenaco/farmacocinética , Adulto , Antiulcerosos/administración & dosificación , Cromatografía de Gases , Cromatografía Líquida de Alta Presión , Diclofenaco/administración & dosificación , Femenino , Semivida , Humanos , Concentración de Iones de Hidrógeno , Masculino , Persona de Mediana Edad , Comprimidos RecubiertosRESUMEN
The bioavailability of diclofenac (D) was assessed in 12 healthy volunteers treated orally with single doses of 100 mg (retard formulation) and subsequently retreated with the same dose of (D) plus sulglicotide (S) 200 mg. (D) blood levels were measured by GLC in samples collected after 1, 2, 4, 6, 8, 12, 24 h. No relevant difference was seen in (D) bioavailability after (S) administration; after 8 h plasma levels of (D) were slightly higher after (S) (p less than 0.05), but this difference can be considered incidental only. Thus, sulglicotide does not interfere with the bioavailability of diclofenac, and can be administered concurrently with the latter to prevent possible gastric injury by the antiinflammatory drug.
Asunto(s)
Antiulcerosos/farmacología , Diclofenaco/farmacocinética , Sialoglicoproteínas/farmacología , Adulto , Disponibilidad Biológica , Interacciones Farmacológicas , Femenino , Humanos , MasculinoRESUMEN
UNLABELLED: We investigated the effects of thyroid hormone modulation on liver injury associated with ischemia-reperfusion (I-R) and cold storage in rats. First, euthyroid and thyroxine (T4)-pretreated rats were exposed in vivo to 20-min global liver ischemia, then 30-min reperfusion. Liver injury was assessed by measuring serum alanine aminotransferase (ALT) levels. Liver concentrations of adenine nucleotides, reduced glutathione (GSH), and oxidized glutathione were evaluated. Second, rats were given the antithyroid drug propylthiouracil (PTU). Livers stored at 0-1 degrees C in Euro-Collins' solution for 20 h were reperfused at 37 degrees C for 15 min. Lactate dehydrogenase (LDH) in the effluent perfusate and bile flow were evaluated during reperfusion. Serum ALT levels increased after ischemia and I-R. ALT increased significantly more in T4-pretreated than in euthyroid rats after ischemia and I-R. Preischemic levels of adenosine triphosphate (ATP) were significantly lower in livers from T4-pretreated than in euthyroid rats (6.22 +/- 0.7 and 11 +/- 0.9 nmol/mg protein, respectively; P < 0.05). After ischemia, liver ATP was similarly reduced in T4-pretreated and euthyroid rats. After reperfusion, ATP partially recovered in euthyroid rats but remained low in T4-pretreated rats (6.7 +/- 1.0 and 1.91 +/- 0.7 nmol/mg protein, respectively; P < 0.05). Preischemic levels of liver GSH decreased to 44% in T4-pretreated rats. After ischemia, GSH decreased similarly in euthyroid and T4-pretreated rats. GSH recovered promptly after reperfusion in euthyroid rats but remained low in T4-pretreated rats (13.9 +/- 3.3 and 3.9 +/- 0.9 nmol/mg protein, respectively; P < 0.02). During reperfusion after cold storage, LDH in effluent perfusate was significantly lower and bile flow higher in livers from PTU-pretreated rats than from euthyroid rats. The histopathological changes observed after I-R and cold storage confirmed the biochemical findings. Our results suggest that T4 administration exacerbates pretransplant liver damage by increasing liver susceptibility to I-R, whereas PTU administration reduces the liver injury associated with cold storage. IMPLICATIONS: We studied the effects of thyroid hormone modulation on liver injury associated with ischemia-reperfusion and cold storage in rats. Thyroxine administration increased susceptibility to ischemia-reperfusion injury, whereas the antithyroid agent propylthiouracil reduced the deleterious effects associated with cold storage.