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1.
Cyclodextrin formulation of dorzolamide and its distribution in the eye after topical administration. 总被引:2,自引:0,他引:2
Hakon H Sigurdsson Einar Stefánsson Elínborg Gudmundsdóttir Thór Eysteinsson Margrét Thorsteinsdóttir Thorsteinn Loftsson 《Journal of controlled release》2005,102(1):255-262
Due to limited aqueous solubility of dorzolamide at physiologic pH, the pH of Trusopt eye drops (cont. 2% dorzolamide) has to be kept at about 5.65, and to increase the topical bioavailability of the drug from Trusopt the contact time of the drug with the eye surface is increased by increasing the viscosity of the eye drops to 100 cps. This low pH and high viscosity can lead to local irritation. In this study, dorzolamide hydrochloride was formulated as 2% and 4% low viscosity solutions (viscosity 3 to 5 cps) containing randomly methylated beta-cyclodextrin at pH 7.45. These formulations were evaluated in rabbits. The animals were sacrificed at various time points after topical administration of the drug and the dorzolamide concentration determined in the different parts of the eye. Trusopt was used as a reference standard. The topical availability of dorzolamide from the cyclodextrin-containing eye drops appeared to be comparable to that from Trusopt and the drug reached retina and optic nerve to give measurable concentrations for at least 8 h after administration of the eye drops. 相似文献
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JA HYEON KU CHEOL KWAK SEUNG-JUNE OH EUNSIK LEE SANG EUN LEE JAE-SEUNG PAICK 《International journal of urology》2004,11(7):489-493
BACKGROUND: Our aims in the present study were to estimate the influences of pain and urinary symptoms on quality of life, and to determine which of these two variables has the most predictive power with respect to quality of life in young men with chronic prostatitis-like symptoms. METHODS: Chronic prostatitis-like symptoms were measured by the National Institutes of Health-Chronic Prostatitis Symptom Index. Of the 28,841 men aged 20 years who lived in the study community, 18,495 men (a response rate 64.1%) agreed to participate in the study. A total of 1057 men who complained of symptoms indicative of chronic prostatitis were included in the study. The influences of pain and urinary symptoms on quality of life were determined using logistic regression analysis. The receiver operating characteristic (ROC) curve was used to estimate the predictive ability of each of these variables with respect to quality of life. RESULTS: Results from multivariate analysis showed that both pain and urinary symptoms were associated with an increased likelihood of impaired quality of life, although pain contributed more to a reduced quality of life than urinary symptoms. Relative to men who experienced mild pain, men who experienced moderate pain had a 3.9-fold risk of poor quality of life (odds ratio [OR], 3.87; 95% confidence interval [CI], 2.86-5.23; P < 0.001) and those who experienced severe pain had a 15.7-fold risk of reduced quality of life (OR, 15.68; 95% CI, 6.59-37.35; P < 0.001). Moderate urinary symptoms were associated with a 1.4-fold risk of bother (OR, 1.41; 95% CI, 1.01-1.99; P < 0.001) and severe urinary symptoms were associated with 2.4-fold risk (OR, 2.39; 95% CI, 1.37-4.12; P < 0.001), relative to mild urinary symptoms. Comparison of the effects of pain and urinary symptoms showed that pain severity had the most predictive power for bother, quality of life, and quality-of-life impact. The areas under the ROC curves for bother, quality of life, and quality-of-life impact were 71.3%, 69.3% and 72.5%, respectively. CONCLUSION: Urinary symptoms and pain might be associated with an increased likelihood of impaired quality of life in young men with chronic prostatitis-like symptoms. In addition, our findings suggest that pain severity is the most influential variable for determining quality of life in this population. 相似文献
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P Ll Sigurdsson Tryggvi Thorvaldsson Sveinbj
Rn Gizurarson Eggert Gunnarsson 《Drug delivery》1997,4(3):195-200
A vast number of potent neuropharmaceuticals, many of which are peptides, are excluded from entry into the brain because of the highly selective blood-brain barrier. The fact that a number of drugs have been shown to be transported directly to the central nervous system following application to the olfactory region of the nose is therefore of major interest. In the present study, the feasibility of delivering peptides to the brain via the olfactory route was assessed using insulin as a model peptide. Systemic hyperinsulinemia induced by subcutaneous injection did not significantly reduce the amount of 125I-insulin transported from the nose to the brain in vivo, which suggests that the impact of systemic absorption on drug transport is minimal. A linear relationship was seen between insulin accumulation in the brain and the dose applied, without any relevant saturation. Contrary to what was expected, both systemic and olfactory absorption of insulin was enhanced when the pH of the medium was near the isoelectric point. The amount absorbed to the brain was found to be linearly related to the net charge of the molecule (r = -0.61; n = 20). It was concluded that insulin gains access to the central nervous system from the olfactory region of the nose by a nonspecific pathway. The olfactory route may therefore become an important means to deliver peptides to the brain. 相似文献
10.
T Abu-Nema K Ayyash L Berntman Y Matani G H Sigurdsson I Francis C Hellekant 《Circulatory shock》1988,24(1):55-62
Two groups (n = 10 in each) of adult sheep were exposed to hemorrhagic shock resulting in mean arterial pressure (MAP) below 25 mmHg for 10 min. Following that, group A received crystalloids (8% of body wt) during one hr together with supraceliac intraaortic balloon tamponade during the first 30 min, while group B (controls) received crystalloids only. The central circulation was rapidly restored in group A, as indicated by increased MAP and increased systemic vascular resistance (SVR). After deflation of the balloon MAP dropped to the same value as in the control group, while cardiac index increased gradually with volume replacement and was significantly higher at the end of the resuscitation period (60 min) than in the control group (P less than 0.05). Despite a more rapid restoration of central hemodynamics in group A, lactic acidosis was more severe, acute renal failure and neurological complications more frequent, and mortality higher than in the control group. It was concluded that continuous supraceliac aortic occlusion for 30 min had deleterious effects on organs dependent on aortic blood flow distal to the aortic tamponade and may contribute to the development of multiple organ failure after resuscitation from hemorrhagic shock. Further studies are needed to evaluate the effects of intermittent intraaortic balloon tamponade in hemorrhagic shock. 相似文献