摘要:

SummaryAlthough the combined administration of atenolol and nifedipine has been shown to be effective in the treatment of angina pectoris the optimum dosage level of the combination has not yet been established. A double-blind, randomly assigned three period cross-over study was carried out therefore to investigate the effects of different daily doses of a fixed combination of 50 mg atenolol and 20 mg sustained-release nifedipine per capsule. Twenty-one patients with stable angina pectoris were randomized, after a 2-week run-in period, to receive treatment for 4 weeks with either 1 capsule twice daily (A), 2 capsules in the morning and 1 in the evening (B), or 2 capsules twice daily (C). A treadmill exercise tolerance test was performed together with a clinical evaluation after the run-in and each of the three treatment periods. Analysis of the results from the 19 patients who completed the study revealed there were no significant differences between the three treatment periods with respect to the general exercise test parameters, number of anginal attacks per week or nitrate consumption. Few side-effects were reported and were only mild in nature. On these findings, therefore, there would appear to be little justification for increasing the dose of the combination above the equivalent of treatment A.

ISSN:0300-7995    

DOI:10.1185/03007999509111549

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

SummaryGarlic (Allium sativum L.) is thought to have a variety of therapeutic applications including inhibition of platelet aggregation. Many of the therapeutic actions of garlic parallel the physiological effects of nitric oxide and may be explained by its ability to increase nitric oxide synthase activity intracellularly. Our studies showed that both water and alcoholic extracts of garlic are very potent inhibitors of platelet aggregation induced by epinephrine and ADP. Similar dilutions of garlic extract also activated nitric oxide synthase activity in isolated platelets in vitro. The same extract was also very effective in activating nitric oxide synthase activity in placental villous tissue. The addition of garlic extracts increased nitric oxide synthase activity in a dose-dependent manner. Nitrite levels in the supernatants of incubated placental villous tissue were similarly increased. Activation of calcium-dependent nitric oxide synthase and the subsequent production of nitric oxide is probably the most novel mechanism yet claimed by which garlic can exert its therapeutic properties.

ISSN:0300-7995    

DOI:10.1185/03007999509111550

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

SummaryIn order to evaluate the pharmacokinetics and excretion of ramipril in man, 8 cholecystectomy patients aged between 53 and 68 years received 5 mg ramipril orally as a single dose. All patients had a T-drain inserted to permit bile collection; all gave their informed consent to participate in the trial. Serum samples were collected half-hourly until 2 hours, then hourly until 6 hours, then at 8, 10, 24 and 25 hours after intake. Urine was collected in 2-hour fractions until 8 hours, followed by a 4-and a 12-hour fraction. Bile was collected hourly until 6 hours, followed by a 6–and a 12-hour collecting fraction. Concentrations of ramipril and ramiprilat in serum, and determinations in urine and bile of ramipril, ramiprilat, ramipril glucuronide, ramiprilat glucuronide, diketopiperazine and diketopiper-azine acid were made; total amounts excreted were calculated. Peak concentrations of ramiprilat in plasma (8.7±1.6 ng/ml) were reached after about 8 hours. AUC0.8and AUC0.24-values were 36.5 and 111.9 ng.h/ml, respectively. Ramiprilat Cmax-concentrations were about 300-fold higher in bile than in plasma, the corresponding difference for ramipril between bile and plasma was about 4-fold. The main fractions excreted in the urine were diketopiperazine acid and ramiprilat amounting to 13.2±5.6 and 4.4±2.4%, respectively, of the dose administered. Only a very small fraction of the dose was excreted with urine as unchanged ramipril, on average 0.9±1.0%. The main fractions excreted in the bile were diketopiperazine acid, ramiprilat glucuronide and diketopiperazine, 9.0±5.3, 3.4±4.2 and 2.0±1.2% in 24 hours, respectively, of the dose administered. Only a negligible fraction of the dose (average 0.1±0.1%) was excreted with bile as unchanged ramipril. In conclusion, there is strong evidence that circulating ramipril and ramiprilat are eliminated by both the liver and the kidneys. For the patients studied it can be estimated from late collection periods that some 2/3 of circulating ramipril and ramiprilat are eliminated by the kidneys and 1/3 eliminated by the liver.

ISSN:0300-7995    

DOI:10.1185/03007999509111551

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

SummaryA study was performed to assess the efficacy and tolerability of rifaximin in the treatment of encephalopathy during cirrhosis of the liver: Fifty-five patients suffering from grade 1, 2 and 3 portosystemic encephalopathy, with a mean age of 58.9 years (range 30 to 86 years) were evaluated. The patients were treated for 15 consecutive days with rifaximin, an antibiotic which is not absorbed by the intestinal wall, at a dosage of 1200 mg/day in association with sufficient lactulose to induce 2 or 3 evacuations per day. Combined use of the 2 drugs proved an efficient means of controlling the majority of signs and symptoms. After just a few days, an improvement in the signs of encephalopathy was noted in all patients. The treatment was well tolerated and the patients completed the trial without any drug-related side-effects. The results of our trial, although in the context of an open assessment, confirm the clinical efficacy of rifaximin in association with a non-absorbable disaccharide such as lactulose. The 2 compounds have a synergetic effect in reducing ammonia-producing flora. Its efficacy and good tolerability make rifaximin a valid alternative to the use of aminoglycoside antibiotics associated with disaccharides in the treatment of patients with liver disease, particularly in the case of prolonged therapy.

ISSN:0300-7995    

DOI:10.1185/03007999509111552

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

SummaryHigh-dose aprotinin is now routinely used in cardiac surgery to reduce postoperative blood loss and transfusion requirements, although several cases of anaphylactic reactions to the proteinase inhibitor have been reported. As part of a multi-centre study to evaluate the immunological response to aprotinin after first exposure 61 cardiac surgical patients were treated with the Hammersmith regimen. Patients with previous aprotinin exposure were excluded from the study. To determine specific IgG and IgE antibodies blood samples were taken pre-operatively, within 3 to 4 weeks and 6 to 7 months after operation. Determinations were made by using Western Blot and ELISA methods. Fifty-six patients were followed up for a 6-month period, 26 (46.4%) of them developed IgG antibodies to aprotinin determined by Western Blot, whereas only 14 (26.8%) patients with IgG antibodies were found by the ELISA. IgE antibodies were not found in any of the patients. On hospital admission and 6 months post-operatively additional intradermal prick tests were performed. No clear-cut positive reaction to the skin test was found in any patient.

ISSN:0300-7995    

DOI:10.1185/03007999509111553

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

SummaryTwo studies were performed—one in elderly, hypertensive patients and one in patients with chronic liver disease - to investigate the effect of age and liver disease upon the pharmacokinetics of nisoldipine, a dihydropyridine-type calcium antagonist. The effect of acute and chronic administration of nisoldipine (once and twice daily) was investigated in 17 elderly hypertensive patients. Compared with previously published data from young healthy volunteers, the values for Cmaxand AUC appear to be higher in elderly hypertensive patients while Tmax, and half-life were unchanged. Nisoldipine significantly reduced both systolic and diastolic blood pressure when given acutely to elderly hypertensive patients. Major alterations in the pharmacokinetics of nisoldipine were found in 7 patients with chronic liver disease when compared with the elderly hypertensives and healthy volunteers. The values for AUC, Cmaxhalf-life and volume of distribution were all higher than expected from the volunteer data while clearance was lower: One patient receiving primidone had very low nisoldipine levels, suggesting that the concomitant administration of agents that may induce the metabolism of nisoldipine should be discouraged. Nevertheless, comparisons of nisoldipine plasma levels after acute and chronic administration showed no evidence of any accumulation in either patient population in the doses used. The drug was generally well tolerated although 1 patient with chronic liver disease was withdrawn due to fluid retention.

ISSN:0300-7995    

DOI:10.1185/03007999509111554

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

ISSN:0300-7995    

DOI:10.1185/03007999509111555

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor