The pharmacokinetics of orally administered ranitidine were studied in 10 patients with endoscopically proved duodenal ulceration after a single 150 mg dose and after 4 weeks 1 ranitidine treatment (150 mg twice daily), at which time there was endoscopic evidence of complete ulcer healing. After a single dose the median elimination half-life was 135 minutes and the median area under the curve (AUC) was l 844 ng/ml.hr. Although the maximum concentration after a single dose (Cmax = 365 ng/ml) was significantly different from that after continuous treatment (Cmax = 562 ng/ml) (p <0,05) there was no significant difference between the minimum concentrations at 12 hours post-dosing (Cmin = 35 ng/ml and 30 ng/ml respectively) and the median half-lives were identical. No accumulation of ranitidine occurred in these patients after 4 weeks' chronic ranitidine treatment. Five patients received 20 mg ranitidine intravenously. The apparent volume of distribution of the central compartment ranged from 10,5 to 28,4 1 while the elimination rate constant β range from 0,34 to 0,78 h⁻¹ with the t½ ranging from 53 to 122 minutes. The mean oral bioavailability was 51%. The pharmacokinetics of ranitidine were studied in a further 7 patients with chronic duodenal ulceration who showed endoscopic evidence of unhealed ulcers after at least 8 weeks' treatment with ranitidine. There were no significant differences in any of the pharmacokinetic parameters when these patients were compared with the 10 responders above after multiple-dosage except that the disposition rate constant was smaller in non-responders (0,24 h⁻¹ compared with 0,31 h⁻¹, p <0,002). Two patients did, however, have very low plasma concentrations with above average basal and maximal acid output which may have contributed to the lack of response to ranitidine treatment. Single- and multiple-dose pharmacokinetic studies of oral ranitidine were carried out in 6 patients with chronic renal failure (RF) (creatinine clearance <25 ml/min) and compared with those obtained for the 10 patients with chronic duodenal ulceration with normal renal function (creatinine clearance >65 ml/min). There appeared to be no significant differences in absorption rate or amount absorbed but the median elimination rate constant was significantly reduced from 0,31 h⁻¹ in controls to 0,14 h⁻¹ in RF (p <0,002) resulting in a two-fold increase in t½ (312 minutes) after a single dose. Cmax did not differ significantly although Cmin and AUC were significantly larger in RF patients (both p <0,002). It is suggested that the dosage of ranitidine be reduced from 150 mg to 75 mg twice daily in severe renal failure although it was not possible to relate half-life, elimination rate constant or AUC directly to creatinine clearance.

Thesis (M.Sc. (Pharmaceutics))--Mahidol University, 2007. / LICL has E-Thesis 0025 ; please contact computer services.

Atualmente a grande malona dos fármacos apresenta grupamento amínico. Estes quando associados à açúcares redutores ou a outros adjuvantes farmacêuticos contendo carbonila, freqüentemente produzem manchas de escurecimento ou descoloração, a Reação de Maillard pode explicar tal ocorrência. Além de poder comprometer a idoneidade do produto. O presente trabalho tem como objetivo estudar o comportamento de xaropes contendo aminas aromáticas, tendo em vista que a associação entre açúcares e aminas podem gerar problemas de estabilidade. Os protótipos escolhidos foram: a metoclopramida, uma benzamida, fármaco que está na terapêutica a bastante tempo com atividade farmacológica antiemética; e a bromexina, composto benzilamino, fármaco que atua no aparelho respiratório com ação expectorante e mucolítica. Amostras dos xaropes de metoclopramida e bromexina foram mantidas em estufa a 40°C por seis meses. A intervalos regulares de tempo, alíquotas foram retiradas e submetidas à analise quantitativa pelo método de Bratton & Marshall, seguida de leitura espectrofotométrica. Não houve grande variação do teor de metoclopramida em relação a concentração de açúcar, uma vez que foram preparadas amostras do xarope de metoclopramida em diferentes concentrações de açúcar. Foi evidenciada a diminuição do teor de metoclopramida, na ordem de 50%, após o período de estocagem, tanto para amostra comercial como para amostra padronizada. Já no xarope de bromexina evidenciou-se a decomposição do fármaco apenas na amostra padronizada, ordem de 50%, enquanto que na amostra comercial não ocorreu decaimento significativo do fármaco, após a estocagem. / Nowadays the great majority of the pharmaceutical drugs has amine group in their structure. These drugs, when associated to sugar reducers, or other carbonile excipients frequently produce darkening stains or fading. The Maillard reaction can explain such occurrence. The reaction can compromise the suitability of the pharmaceutical dosage forms. The present work has as objective to study the behavior of syrups containing aromatic amines. It is known that association of sugars and amines can generate problems of stability. The chosen prototypes were: the metoclopramide hydrochloride, a benzamide, drug that has been in the therapeutics over thirty years, with antiemetic pharmacology activity; and the bromhexine hydrochloride, a benzilamine drug, that acts in the breathing apparel, with expectorant and mucolitic. Samples of the metoclopramide and bromhexine syrups were maintained in stove at 40°C for six months. In regular time intervals aliquots were removed and submitted to quantitative determination by the Bratton & Marshall\'s method, followed by a spectrophometric method determination. There was not great variation of the metoclopramide level in relation to sugar level, once syrup metoclopramide samples were prepared in different sugar leveI. There was a decrease of the metoclopramide level, over 50%, after a period in stove, for commercial sample and for standardized sample. In the bromhexine syrup drug\'s decomposition was evidenced in the standardized sample only, over 50%, while in the commercial sample significant drug\'s decline have not been found, after the time in stove.

Atualmente a grande malona dos fármacos apresenta grupamento amínico. Estes quando associados à açúcares redutores ou a outros adjuvantes farmacêuticos contendo carbonila, freqüentemente produzem manchas de escurecimento ou descoloração, a Reação de Maillard pode explicar tal ocorrência. Além de poder comprometer a idoneidade do produto. O presente trabalho tem como objetivo estudar o comportamento de xaropes contendo aminas aromáticas, tendo em vista que a associação entre açúcares e aminas podem gerar problemas de estabilidade. Os protótipos escolhidos foram: a metoclopramida, uma benzamida, fármaco que está na terapêutica a bastante tempo com atividade farmacológica antiemética; e a bromexina, composto benzilamino, fármaco que atua no aparelho respiratório com ação expectorante e mucolítica. Amostras dos xaropes de metoclopramida e bromexina foram mantidas em estufa a 40°C por seis meses. A intervalos regulares de tempo, alíquotas foram retiradas e submetidas à analise quantitativa pelo método de Bratton & Marshall, seguida de leitura espectrofotométrica. Não houve grande variação do teor de metoclopramida em relação a concentração de açúcar, uma vez que foram preparadas amostras do xarope de metoclopramida em diferentes concentrações de açúcar. Foi evidenciada a diminuição do teor de metoclopramida, na ordem de 50%, após o período de estocagem, tanto para amostra comercial como para amostra padronizada. Já no xarope de bromexina evidenciou-se a decomposição do fármaco apenas na amostra padronizada, ordem de 50%, enquanto que na amostra comercial não ocorreu decaimento significativo do fármaco, após a estocagem. / Nowadays the great majority of the pharmaceutical drugs has amine group in their structure. These drugs, when associated to sugar reducers, or other carbonile excipients frequently produce darkening stains or fading. The Maillard reaction can explain such occurrence. The reaction can compromise the suitability of the pharmaceutical dosage forms. The present work has as objective to study the behavior of syrups containing aromatic amines. It is known that association of sugars and amines can generate problems of stability. The chosen prototypes were: the metoclopramide hydrochloride, a benzamide, drug that has been in the therapeutics over thirty years, with antiemetic pharmacology activity; and the bromhexine hydrochloride, a benzilamine drug, that acts in the breathing apparel, with expectorant and mucolitic. Samples of the metoclopramide and bromhexine syrups were maintained in stove at 40°C for six months. In regular time intervals aliquots were removed and submitted to quantitative determination by the Bratton & Marshall\'s method, followed by a spectrophometric method determination. There was not great variation of the metoclopramide level in relation to sugar level, once syrup metoclopramide samples were prepared in different sugar leveI. There was a decrease of the metoclopramide level, over 50%, after a period in stove, for commercial sample and for standardized sample. In the bromhexine syrup drug\'s decomposition was evidenced in the standardized sample only, over 50%, while in the commercial sample significant drug\'s decline have not been found, after the time in stove.

Wang, Zexi. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 63-64). / Abstract --- p.i / Acknowledgement --- p.iii / Chapter 0 --- Introduction --- p.1 / Chapter 1 --- The Design of the Experiments --- p.4 / Chapter 1.1 --- Flies and the Devices --- p.5 / Chapter 1.2 --- Parameter Settings and Interested Information --- p.8 / Chapter 2 --- Video Processing --- p.11 / Chapter 2.1 --- "Videos, Computer Vision and Image Processing" --- p.11 / Chapter 2.2 --- Details in Video Processing --- p.14 / Chapter 3 --- Data Analysis --- p.20 / Chapter 3.1 --- Background --- p.20 / Chapter 3.2 --- Outline of Data Analysis in Our Project --- p.22 / Chapter 4 --- Effect of the Medicine --- p.25 / Chapter 4.1 --- Hypothesis Testing --- p.26 / Chapter 4.2 --- Two-sample t Test --- p.28 / Chapter 5 --- Significance of the Two Factors --- p.32 / Chapter 5.1 --- Background of ANOVA --- p.33 / Chapter 5.2 --- The Model of ANOVA --- p.35 / Chapter 5.3 --- Two-way ANOVA in Our Data Analysis --- p.42 / Chapter 6 --- Regression Model --- p.45 / Chapter 6.1 --- Background of Regression Analysis --- p.47 / Chapter 6.2 --- Polynomial Regression Models --- p.52 / Chapter 6.2.1 --- Background --- p.52 / Chapter 6.2.2 --- R2 and adjusted R2 --- p.53 / Chapter 6.3 --- Model Verification --- p.58 / Chapter 6.4 --- A Simpler Model As the Other Choice --- p.59 / Chapter 6.5 --- Conclusions --- p.60 / Chapter 7 --- Further Studies --- p.61 / Bibliography --- p.62

Policy makers in education and international development have lately gravitated toward the randomized controlled trial (RCT)—an evaluation design that randomly assigns a sample of people or households into an intervention group and a control group in order to measure the differential effect of the intervention—as a means to determine program impact. As part of federal regulations, the U.S. Department of Education and the U.S. Agency for International development explicitly declared a preference for the RCT. When advocating for adopting the RCT model as the preferred evaluation tool, policy makers point to the success story of medical trials and how they revolutionized medicine from Medieval charlatanry to a modern life-saving discipline. By presenting a more nuanced account of the role of the RCT in medical history, however, this study finds that landmark RCTs were accompanied with challenges, Evidence-Based Medicine had rightful critics, and opportunistic biases in drug trials apply equally to education policy and international development. This study also examines the recent privileged role of the RCT in education and international development, concluding that its initial promise was not entirely born out when put into practice, as the national Reading First Initiative exemplifies. From a comparative perspective, the RCT movements also encountered major RCT critics, whose voices were not initially heard. These voices, however, seem to have contributed to a swing of the pendulum away from RCT primacy back towards greater methodological pluralism. A major conclusion of this study is that policy makers should exercise great caution when using RCTs as a policy evaluation tool. This conclusion is arrived at via considering RCT biases, challenges, and limited generalizability; understanding its interpretive-qualitative components; and broadening the overall methodological repertoire to better enable evaluations of macro-policy interventions. / text

Tuberculosis is a fatal airborne disease caused by bacteria from the Mycobacterium tuberculosis complex (MTBC). The incidence of contracting tuberculosis is estimated to be around 10.6 million cases each year. Increased drug resistance among mycobacteria has led to the need to develop new treatments. The study's purpose was to determine the antimycobacterial ability of drug complexes and how toxic these complexes are against human cells. Drug complexes from "phage derived endolysins" and "A pyrazine amide-4 aminoquinoline hybrids" were studied to possibly be included as a treatment against tuberculosis in the future. The minimum inhibitory concentrations (MIC) of the drug complexes were analyzed by the method Resazurin microtiter assay (REMA), where the results were assessed visually. The toxicity of the drug complexes was studied by growing THP1-Blue™ NF-κB cells, which then were exposed to the drug complexes. The results could then be obtained by absorbance measurement with spectrophotometry. One-way ANOVA showed a non-significant value, as the P-value was 0.44 (P&gt;0.05). However, more supplementary studies need to be carried out to obtain a significant result. All performed concentrations of the drug complexes were assessed as non-toxic against human THP1-Blue™ NF-κB cells. / Tuberkulos är en dödlig luftburen sjukdom som orsakas av bakterier från Mycobacterium tuberculosis complex (MTBC). Den årliga incidensen i världen för insjuknande i tuberkulos beräknas vara 10.6 miljoner. Ökad läkemedelsresistens bland mycobakterier har lett till att nya behandlingar behöver utvecklas. Syftet med studien var att studera två olika läkemedelskomplex antimycobakteriella förmåga samt hur toxiska dessa komplex är mot humana celler. Läkemedelskomplex från "phage derived endolysins" och "A pyrazine amide-4 aminoquinoline hybrids" studerades för att eventuellt kunna ingå som behandling mot tuberkulos framöver. Läkemedelskomplexens minsta inhibitoriska koncentration (MIC) analyserades genom metoden Resazurin microtiter assay (REMA) där resultaten bedömdes visuellt. Läkemedelskomplexens toxicitet studerades genom odling av THP1-Blue™ NF-κB celler som sedan exponerades för läkemedelskomplexen och resultaten  kunde sedan fås genom absorbansmätning med spektrofotometri. One-way ANOVA påvisade ett icke-signifikant värde,  då p-värdet blev 0,44 (P&gt;0,05). Dock behövs fler kompletterande studier genomföras för att studera detta ytterligare. Alla studerade koncentrationer av läkemedelskomplexen bedömdes vara icke-toxiska mot humana THP1-Blue™ NF-κB celler.

The efficacy and safety of oral nadolol in supraventricular tachycardia were evaluated prospectively in 27 children (median age 5.5 years). Fifteen patients had an unsuccessful trial of digoxin therapy. Intravenous nadolol was given to seven patients during electrophysiologic study; five of these had an excellent response and two had a partial response (25% decrease in tachycardia rate). Six of these patients had a similar response to oral nadolol. Twelve patients received both propranolol and nadolol. Among six patients, intravenous propranolol was successful in four and unsuccessful in two; all six had a similar response to oral nadolol. With oral propranolol, tachycardia was well controlled in four patients and persistent in two; five of five patients had a similar response to oral nadolol. Twenty-six patients were treated with oral nadolol; the arrhythmia was well controlled in 23, 2 had recurrent tachycardia and 1 patient had tachycardia at a 25% slower rate. The effective dose of nadolol ranged between 0.5 and 2.5 mg/kg body weight once daily (median dose 1 mg/kg per day). During follow-up (3 to 36 months), compliance and tolerance were excellent; excluding 2 patients with reactive airway disease who developed wheezing, only 3 (12%) of 24 had side effects necessitating a change in drug therapy. Once a day nadolol is a safe and effective agent in the management of supraventricular tachycardia in children. Its long-term efficacy can be predicted by the short-term response to intravenous nadolol or propranolol during programmed electrophysiologic study.

Paraplegia or paraparesis caused by temporary cross-clamping of the aorta is a devastating sequela in patients after surgery of the thoracoabdominal aorta. No effective clinical method is available to protect the spinal cord from ischemic reperfusion injury. A small animal (rat) model of spinal cord ischemia is established to better understand the pathophysiological events and to evaluate potential treatments. Eighty-one male Sprague-Dawley rats weighing 300 g to 350 g were used for model development (45) and treatment evaluation (36). The heparinized and anesthetized rat was supported by a respirator following tracheostomy. The thoracic aorta was cannulated via the left carotid artery for post-clamping intra-aortic treatment solution administration. After thoracotomy, the aorta was freed and temporarily clamped just distal to the left subclavian artery and just proximal to the diaphragm for different time intervals: 0, 5, 10, 15, 20, 25, 30, 35, and 40 minutes (five animals per group). The motor function of the lower extremities postoperatively showed consistent impairment after 30 minutes clamping (5/5 rats were paralyzed), and this time interval was used for treatment evaluation. For each treatment, six animals per group were used, and direct local intra-aortic infusion of physiologic solution (2 mL) at different temperatures with or without buffer substances was given immediately after double cross-clamp to protect the ischemic spinal cord. Arterial blood (2 mL) was infused in the control group. The data indicate that the addition of HCO3-(20 mM) to the hypothermic (15 degrees C) solution offered complete protection of the spinal cord from ischemic injury.(ABSTRACT TRUNCATED AT 250 WORDS)