摘要:

Abstract:The effects of amrinone on conduction in the intact canine heart were studied. Intracardiac His‐electrode catheter recordings were used to measure the functional refractory period (FRP) of the AV node and conduction time through the AV node (A2H2interval) and in the His‐Purkinje system (H2V2interval). Amrinone (2.5 to 10 mg/kg) shortened the FRP and A2H2in a dose‐dependent manner but had no significant effect on H2V2. In hearts where AV conduction was depressed by treatment with verapamil, propranolol, or ouabain, amrinone partially reversed this depression. Amrinone also shortened the recovery time of spontaneous sinoatrial (SA) node activity following a train of rapid atrial stimulation. This effect was also observed after depression of SA nodal recovery with verapamil, propranolol, or ouabain. These results indicate that amrinone enhances AV conduction and SA nodal activity in the normal heart and may favorably influence depressed AV conduction and SA nodal activity induced by a variety of cardioactive a

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02733.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:Radioreceptor and high‐performance liquid chromatographic (HPLC) assays for nitrendipine were developed and applied to the analysis of serum samples. The HPLC assay required both extraction and concentration of the serum samples, whereas the radioreceptor assay involved only direct dilution of the serum. The HPLC assay, in contrast to the radioreceptor assay, can be used for detection and quantitative analysis of biologically inactive metabolites. The radioreceptor assay is based on the competition between nitrendipine in serum and [3H]nitrendipine for high‐affinity binding sites on cardiac membranes. Forty‐two serum samples were obtained from five volunteers, and the HPLC and radioreceptor assay results were compared. A correlation coefficient of 0.98 was found between the results of the two assays within the nitrendipine serum concentration range of 1 to 20 ng/ml. No significant levels of active metabolites or any other interferences were found. The radioreceptor assay provides a specific and sensitive alternative to HPLC; it is rapid and inexpensive and with minor modifications may be applicable to most presently available Ca2+channel antago

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02734.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:Dialysis clearance and drug recovery of theophylline were investigated in three peritoneal dialysis patients and the results were compared with those obtained from five hemodialysis patients. Peritoneal clearance averaged 9.5 ml/min, in contrast with the hemodialysis clearance of 84.8 ml/min, indicating a relative inefficiency of peritoneal dialysis with regard to theophylline removal. Theophylline half‐life was reduced substantially during hemodialysis, 2.0 to 3.2 hours, in comparison with the normal half‐life range of 4.7 to 6.8 hours during peritoneal dialysis. The fraction of theophylline recovered by peritoneal dialysis approximated 3.2 per cent of dose, while hemodialysis recovered up to 40 per cent of the administered dose. The overall observations of half‐life, dialysis clearance, and drug recovery suggest a clear advantage of hemodialysis over peritoneal dialysis for theophylline detoxification. However, peritoneal dialysis may be preferred to hemodialysis for uremic patients requiring theophylline therapy. Since the removal of theophylline by peritoneal dialysis is minimal, an undesirable alteration of the theophylline dosage regimen in association with dialysis therapy can thus be av

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02735.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02736.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02737.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02738.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:Data from over 1000 patients with rheumatoid arthritis who received tolmetin sodium in double‐blind and open studies have been pooled to assess long‐term efficacy and safety. Duration of the studies was 12 weeks to 48 months. Mean age of patients was 54 years; ratio of males to females was 1:3. The results showed that tolmetin provided rapid onset of action and continuous progressive decrease in symptoms in all measurements of inflammation. Mean number of painful joints was reduced from 22 at baseline to 16 at one month, to 9 at one year, and to 6 at two years. Duration of morning stiffness was 155 minutes at baseline, 123 minutes at one month, 74 minutes at one year, and 78 minutes at two years. The final global evaluation by the investigators showed that 61 per cent of patients had a marked or moderate response. Mean erythrocyte sedimentation rates did not increase during therapy with tolmetin. Initial dose of tolmetin in the patients pooled for this analysis was generally 600 to 800 mg/day, and the mean dose throughout the study was 1256 mg/day. The drug was well tolerated overall. As anticipated, gastrointestinal symptoms were the most frequently reported; nausea was experienced by 13 per cent of the patients at some time during therapy, and gastrointestinal distress, dyspepsia, or abdominal pain was reported by approximately 8.6 per cent each. Only 12.7 per cent of patients discontinued tolmetin because of untoward reactions; 15.9 per cent of patients discontinued because of insufficient therapeutic response. The results of these long‐term studies of patients with rheumatoid arthritis demonstrated that tolmetin is an effective antiinflammatory agent with an acceptable record of s

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02739.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:The efficacy and safety of tolmetin sodium in the management of ankylosing spondylitis are presented in a review of published and unpublished data. In both open and controlled clinical studies, tolmetin was superior to placebo and equal to indomethacin in its capacity to relieve pain, inflammation, and other symptoms of ankylosing spondylitis (AS). Objective and subjective assessments showed that both tolmetin sodium and indomethacin provided significant therapeutic benefits to patients with AS. In AS, the two drugs showed similar adverse reaction profiles. Adverse reactions with both drugs were minimal and predominantly affected the gastrointestinal tract, in most cases these symptoms cleared spontaneously without discontinuing the drugs.

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02740.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:In order to evaluate the effectiveness and safety of tolmetin sodium in the treatment of both rheumatoid arthritis (RA) and osteoarthritis in geriatric patients, a retrospective study was made of patients 65 years and older who participated in long‐term, controlled, double‐blind and open trials during both the investigational period and since marketing of the drug. Standard entrance criteria, methods of evaluating disease activity, and statistical methods were used in the study of both arthritic diseases. A total of 847 geriatric patients were studied for periods of up to one year; 171 had RA, while 676 had osteoarthritis of large or small joints. Average daily dose of tolmetin sodium was 1141 mg for patients with RA and 953 mg for patients with osteoarthritis. The results of this retrospective study of both RA and osteoarthritis patients show that tolmetin was as effective in geriatric patients as in nongeriatric patients. Symptoms responded rapidly to treatment with tolmetin, and both the inflammatory symptoms of RA and the joint pain and functional parameters of osteoarthritis showed improvement that was both statistically and clinically significant throughout the major course of therapy. Tolmetin was also found to be safe and well tolerated by the elderly patient population. The major complaints were gastrointestinal, but serious or limiting side effects occurred in few patients. The dropout rates due to adverse effects during the entire year of therapy were 15.8 per cent in the RA population and 15.4 per cent in osteoarthritis patients. This retrospective evaluation of tolmetin therapy shows significant relief of the symptoms of both RA and osteoarthritis in a geriatric population and fails to reveal any unusual or serious conditions which would contraindicate its use in the elderly patient. Tolmetin, which is an antiinflammatory agent with a short half‐life, can provide adequate, safe therapy in the geriatric popul

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02741.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:The in vitro effect of tolmetin on deficient T‐lymphocytes from patients with autoimmune diseases was tested using a mitogen‐stimulation assay. For comparison, levamisole was also tested on T‐cells in the same assay system in this group of patients. Tolmetin and levamisole both showed enhancement of T‐cell function and normalization of mitogenesis in vitro. To evaluate the relevance of these in vitro findings to treatment of disease, four patients who had active rheumatoid arthritis and who had displayed repeated deficiency in vitro of T‐cell mitogenesis were studied. After baseline studies, the patients were started on tolmetin at an oral dose of 800 mg/day in divided doses. If no significant enhancement of T‐cell function was observed by four weeks, the dose of tolmetin was increased to 1600 mg/day. The results of the clinical study confirmed that tolmetin enhanced T‐cell function in vivo as well as in vitro in a manner similar to that which has been reported for levamisole. This normalization of T‐cell function by tolmetin was associated with clini

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02742.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY