ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb02754.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:Normally menstruating young female volunteers with no evidence of cardiovascular disease participated in a controlled study of digoxin effects on serum thyroid stimulating hormone (TSH) and prolactin levels in the basal state and after stimulation with thyrotropin releasing hormone (TRH). In the first study, subjects received oral digoxin, 0.5 mg daily, or matching placebo, on days 10 through 22 of a menstrual cycle, then crossed over to placebo or digoxin for days 10 through 22 of the next cycle. Basal serum TSH and prolactin on days 7 through 9 and 20 through 22 did not differ significantly between placebo and digoxin cycles. Levels of both hormones rose after a 200‐μg intravenous dose of TRH given on days 8 and 21, but the response to TRH did not differ between placebo and digoxin cycles. In the second study, subjects received 0.5 mg intravenous digoxin daily for days 7 through 21 of a menstrual cycle. Basal serum TRH and prolactin did not change significantly in response to digoxin. The findings suggest that hormonal changes associated with digoxin therapy, if they exist, are more likely to reflect direct effects on the target organ rather than indirect effects on the hypothalamic‐pituitary

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb02755.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:A phase II double‐blind placebo‐controlled, randomized dose‐ranging trial was undertaken to determine the antiemetic efficacy and toxicity of the synthetic cannabinoid levonantradol at doses of 0.5, 1.0, 1.5, and 2.0 mg. Intramuscular levonantradol was prophylactically administered in random dosing to 20 subjects with a documented history of refractory emesis due to chemotherapy in advanced cancer. The selected dose was administered prior to the chemotherapy and was serially repeated over 12 hours, and efficacy and toxicity data were evaluated for 24 hours. Significant (P<0.01) antiemetic activity over placebo was observed with all doses of levonantradol administered, and a dose‐effect response was not observed. Doses up to 2.0 mg were well tolerated, and observed toxicity increased with increased doses and with repeated dosing. Psychomimetic effects were mild and tolerable, and the limiting side effects were somnolence and hypo

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb02756.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:Ketoprofen, 25, 50, and 100 mg, was compared with 90 mg codeine and placebo for relief of pain due to removal of impacted third molar teeth. Treatment was self‐administered as a single oral dose under double‐blind conditions in five parallel groups established by a random code in healthy young adults. Based on 129 patient evaluations of pain experience and pain relief, ketoprofen was shown to have a more rapid onset and longer duration of action than codeine. In the derived variables of SPID (Sum of Pain Intensity Differences) and TOPAR (Total Pain Relief), all three doses of ketoprofen, with no dose‐related differences among them, were found to provide statistically superior analgesia to codeine and placebo. All five treatments were associated with some adverse reac

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb02757.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:The effects of three beta blockers on liver blood flow and hepatic enzyme activity were investigated. Eight healthy subjects received placebo, 100 mg metoprolol, 40 mg nadolol, and 60 mg propranolol orally three times a day for four days in a randomized block design. On the fourth day of each treatment, beta blockade was measured by inhibition of exercise‐induced tachycardia and apparent liver blood flow was measured by indocyanine green clearance. Plasma concentrations of the beta blockers were measured 2 hours after the early morning dose. Metoprolol produced the greatest inhibition of exercise tachycardia. All three drugs appeared to reduce liver blood flow, but this was only statistically significant in the case of propranolol. Enzyme inhibition occurred but to a varying extent. Propranolol produced a 36 per cent fall in antipyrine clearance (P<0.1) while metoprolol and nadolol both caused a 12 per cent reduction (P<0.05 andP= 0.06, respectively). Wide interindividual variation in the plasma concentrations of the drugs limit interpretation, but the results suggest that at the doses used, metoprolol and nadolol may be less likely to cause significant drug interaction by enzyme inhibition than propranolo

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb02758.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:Twelve healthy male volunteers were treated with 1200 mg/day cimetidine, 300 mg/day ranitidine, or no H2‐receptor antagonist (control) tor seven days in a sequence determined by Latin‐square design. Each treatment period was separated by a seven‐day washout. On the third day of each treatment period, 80 mg propranolol every 12 hours for nine doses was initiated. Whole blood concentrations of propranolol and 4‐hydroxypropranolol were measured at 12 time points during the 12‐hour period following administration of the last propranolol dose. Heart rate was measured before each blood sample was withdrawn. Cimetidine treatment was associated with a 47 per cent increase in the area under the propranolol concentration‐time curve and a 17 per cent increase in elimination half‐life of propranolol. Ranitidine had no significant effect on the concentration‐time profile of propranolol. There were no significant differences in the 4‐hydroxypropranolol pharmacokinetic parameters during any of the treatments. There was, however, a significant decrease in the average 4‐hydroxypropranolol‐to‐propranolol steady‐state concentration ratio during the cimetidine treatment. There was no significant difference in heart rate between any of the treatments. The elevation of propranolol concentrations during cimetidine treatment is likely due to metabolic

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb02759.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:Sixteen healthy volunteers were given either oral or intravenous doses of aminophylline (125 mg) at 9:00a.m.and 9:00p.m.under controlled food conditions. Measured at regular time intervals by homogeneous enzyme immunoassay, the plasma theophylline concentrations 1.5 and 2 hours after oral aminophylline were significantly higher in the morning than in the evening (P<0.05). Also, the mean peak plasma concentration was significantly higher (P<0.05) and the time to peak concentration was faster (P= 0.02) after the morning dose. Neither the morning mean elimination half‐life nor the morning mean area under the plasma concentration‐time curve differed significantly from those after the evening dose. After intravenous aminophylline, no significant differences were found in the plasma theophylline concentrations and in the elimination half‐life between morning and evening. Therefore, the small but statistically significant time‐dependent differences in theophylline kinetics must be due to changes in absorption from the gastrointestinal tract and not to changes in distribution or elimination of t

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb02760.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:Twelve normal subjects each received single 300‐, 600‐, and 1200‐mg oral doses of oxaprozin according to a three‐period crossover design. Total drug plasma concentrations did not increase in proportion to the dose administered. Total clearance (Clo) and volume of distribution (Vd) increased with dose, though elimination t1 2remained unchanged. The fraction of unbound oxaprozin in plasma (fup) varied linearly with total plasma concentration: it increased from 0.068 per cent at 10 μg/ml to 0.180 per cent at 170 μg/ml. A parameter f̂upwas therefore introduced to express the average degree of unbound drug plasma for a given dose, and to allow the calculation of unbound volume of distribution (Vdu) and intrinsic clearance (Cli) as if binding were constant. Even though f̂upincreased with dose, the overall binding in the body (f̂ub∼0.52 per cent) was relatively stable. Neither Vdunor Clichanged with dose; hence, unbound oxaprozin kinetics can be considered to be linear. Protein binding had no effect on unbound oxaprozin plasma levels within the given dose range, and there was a one‐to‐one proportionality between the dose administered and the unbound drug conce

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb02761.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:Seven adult, morbidly obese patients scheduled for bariatric surgery were studied in an identical manner preoperatively and postoperatively. Six patients underwent gastroplasties, and one patient underwent a gastric bypass procedure. A single 250‐mg dose of erythromycin as a Filmtab was administered orally after an overnight fast. Multiple venous blood samples were collected over a 12‐hour period. After surgery, each patient had a decrease in peak concentration and an increase in the time to reach peak concentration compared to presurgery values. Mean peak concentration was reduced from 1.04 μg/ml preoperatively to 0.55 μg/ml postoperatively, and the mean time to peak increased from 3:9 hours to 6.7 hours. Mean weight‐corrected AUC was reduced 41 per cent, with two patients having no detectable serum levels postoperatively. The results suggest that the erythromycin product evaluated is of questionable value for use in bariatric surgery p

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb02762.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:The pharmacokinetics of cyclosporine were studied in five liver transplant patients when they were on and off hemodialysis. There was no significant difference in the blood clearance of cyclosporine between these two periods. Less than 1 per cent of the dose of cyclosporine was recovered in the dialysate. The mean dialysis clearance was less than 1 ml/min. This represents less than 1 per cent of the total blood clearance of cyclosporine. Dosage alterations of cyclosporine during or after hemodialysis do not appear to be necessary.

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb02763.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY