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PILAR CALVO MARÍA J. ALONSO JOS L. VILA-JATO JOSEPH R. ROBINSON 《The Journal of pharmacy and pharmacology》1996,48(11):1147-1152
The ability of different drug carriers to improve the ocular bioavailability of drugs was investigated in the rabbit eye. The assayed drug carriers were suspensions of nanoparticles, nanocapsules and microparticles made of poly-ε-caprolactone (PECL) and a submicron emulsion. Results indicated that the three submicron systems, nanoparticles, nanocapsules and emulsion, increased more than 3-fold the indomethacin concentration in the cornea, aqueous humour and iris-ciliary body at 0.5 and 1 h post-instillation. Furthermore, an increased indomethacin ocular bioavailability of 300% was observed after instillation of the submicron systems in comparison with the value obtained for a commercial solution. In contrast, the microparticles hardly increased the ocular bioavailability of indomethacin. The mechanism of interaction of the colloidal carriers with the corneal epithelium was investigated by confocal laser scanning microscopy. Confocal images indicated that submicron particles penetrate into the corneal epithelium cells by an endocytic mechanism. The similar behaviour of the three colloidal carriers suggests that any of their specific ingredients (PECL, lecithin and oil) acts as a penetration enhancer or an endocytotic stimulator. On the other hand, the favourable ocular penetration of indomethacin when encapsulated in the colloidal carriers, but not in the microparticles, led us to assume that the colloidal nature of these carriers is the main factor responsible for the increased ocular bioavailability of indomethacin. PECL nanoparticles and nanocapsules as well as submicron emulsions are shown to be novel corneal drug carriers, thus representing a useful approach for increasing the ocular bioavailability of drugs. 相似文献
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PILAR ESPANA M.D. DIEGO FIGUERA M.D. † JOSE-MARIA FERNANDEZ DE MIGUEL M.D. † ALBERTO ANAYA M.D. ‡ JOSEFA MENENDEZ M.D. ‡ ALBERTO DURANTEZ M.D. 《The American journal of gastroenterology》1980,73(1):28-32
Three cases of membranous obstruction of the inferior vena cava (IVC) are presented. Two of them underwent transcardiac membranotomy with good results. The third patient was treated symptomatically and died from gastrointestinal hemorrhage and hepatic coma two years after the diagnosis of Budd-Chiari syndrome. At autopsy, membranes were found in the inferior vena cava and hepatic veins. Differentiation of Budd-Chiari syndrome secondary to the presence of such a membrane is essential since these patients are potentially curable by surgical treatment. Cavography visualizes the obstruction and is the procedure of choice for diagnosis of this condition. Surgical treatment with transcardiac membranotomy is effective. Some hepatic abnormalities regress after surgery. Prophylactic postoperative treatment with diuretics seems advisable in these patients to prevent congestive cardiac failure. 相似文献
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PILAR BUSTAMANTE BEGO
A ESCALERA ALFRED MARTIN EUGENIO SELLES 《The Journal of pharmacy and pharmacology》1993,45(4):253-257
Abstract— A modification of the extended Hildebrand equation is proposed to estimate the solubility of an organic drug in solvent mixtures. The equation accurately reproduces the solubility of four sulphonamides in dioxane-water mixtures without requiring the heat of fusion of the solute. A single equation is obtained for predicting the solubility of related drugs using the solubilities of the drugs in the pure solvents, dioxane and water, and solute-solvent interaction terms consisting of the solubility parameter, δ2, of the solute and the solubility parameter, δ1, and basic partial solubility parameter, δ1b, of the solvent mixture. By this procedure a single equation was obtained to estimate the solubilities of three xanthines in dioxane-water and another equation to obtain the solubilities of four sulphonamides. The equation obtained for sulphonamides is able to predict the experimental solubilities of two parent compounds, sulphasomidine and sulphathiazole, and the solubilities of a drug of different structure, p-hydroxybenzoic acid. This suggests that the intermolecular solute-solvent interaction of sulphonamides and p-hydroxybenzoic acid are similar. The results indicate that the solubility behaviour of drugs having different structures may be modelled using a common equation provided that they show similar solute-solvent interactions. 相似文献
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JUAN F. HONEYMAN M.D. LEONARDO SÁNCHEZ M.D. PILAR VALDÉS M.D. 《International journal of dermatology》1995,34(8):583-588
Background. Severe forms of psoriasis have been treated successfully with cyclosporine A (cyA) in Europe and North America. The aim of the present investigation was to record and evaluate this drug treatment in Latin American patients with severe psoriasis in a multicenter controlled dose-efficacy study. Patients and Methods. One hundred and fifty-two patients from 10 Latin American countries had on entry to the study a Psoriasis Area Severity Index (PASI) of 18 or more. Initial treatment was with cyA, 2.5 mg per kg per day for 6 weeks. At week 6, 27 patients with a baseline PASI score reduction of < 33% had the dose increased to 4 mg/kg/day. At week 12, 48 patients, who had not improved their baseline PASI scores by 66% or more, had their dose increased to 4 or 5 mg/kg/day, respectively. At the end of the study, 74 patients (56%) received cyA 2.5 mg/kg/day, 41 patients (31%) received 4 mg/kg/day, and 16 patients (12%) received 5 mg/kg/day. Results. Cyclosporine A treatment was considered successful in 84.7% of the patients, who reduced their initial PASI score by 66% or more at the end of treatment at week 18. Adverse effects were seen in 29 patients (19%). Hypertension occurred in 27% and an increase of serum creatinine level above 30% of the initial value in 40% of patients. Among other side effects were gastrointestinal complaints (5.1%), hirsutism (4.3%), muscle pain (2.2%), joint pain (2.2%), respiratory infections (2.2%), headache (1.4%), and hemorrhagic gingivitis (0.7%). Twenty-one patients (13.8%) were withdrawn from the study for various reasons: adverse events in five cases (3.3%), noncompliance in five cases (3.3%), lack of efficacy in three cases (2%) and nonrelated diseases in two cases (1.3%). There were also six patients of a group that finished earlier than planned. A follow-up at 8 weeks after treatment was performed in 106 patients; in this phase 60 patients (56.5%) continued with their previous successful PASI reduction. Relapses (i.e., PASI increasing by more than 50% over baseline) were seen in 22.6% of cases. Conclusions. Cyclosporine A is an effective and well-tolerated treatment for severe psoriasis. An initial dose of 2.5 mg/kg/day is recommended. Most of the patients have a good response to this dose. 相似文献