摘要:

Abstract:The short‐ and intermediate‐term actions, as well as the carryover and withdrawal effects, of quazepam, a new benzodiazepine hypnotic with a half‐life of 60 to 100 hours, were compared with those of triazolam, a triazolodiazepine hypnotic with a half‐life of 2 to 3 hours. Both the subjective effects of these drugs as well as their objective actions on the sleep EEG were sought. The study was conducted on two groups of six subjects with chronic insomnia who ranged in age from 32 to 56 years. Each subject was studied for 25 consecutive nights. Placebo was administered at bedtime on the first four nights, followed by 30 mg quazepam or 0.5 mg triazolam on the next 14 nights and by placebo again on the ensuing seven withdrawal nights. Both drugs increased the total sleep time during their administration and improved the subjective quality of sleep. Major differences, however, were observed on withdrawal. A significant and marked decrease in the total sleep time occurred with triazolam on the first withdrawal night. With quazepam, rebound insomnia was not observed at any time during the seven‐day withdraw

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb02767.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:CGS‐13080 is a new potent selective inhibitor of thromboxane synthetase. This study reports the results of a safety and efficacy study of single oral doses in normal healthy volunteers. The compound was well tolerated by all subjects without evidence of any adverse reactions. Serum thromboxane B2levels (the stable metabolic product of thromboxane A2) were significantly reduced after administration of the compound, with the maximal effect of a 99 per cent reduction occurring at 0.5 and 1 hour after administration. There was a concomitant increase in PGE2and 6‐keto‐PGF1α(the stable metabolic product of PGI2), suggesting a shunting of cyclic endoperoxide metabolism. The apparent half‐life of the compound is about 1 hour, but return to 50 percent of the original thromboxane B2levels was achieved between 4 and 6 hours. Platelet aggregation to collagen and bleeding times failed to demonstrate significant changes after drug administration. Bleeding times showed a slight increase 2 hours after administration of the

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb02768.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:An investigation was undertaken to test whether the dose‐response curve of a cholecystokinin‐like agent (ceruletide) could be established by administering it in graded doses sequentially on the same day. The results were compared to individual doses given on separate days. The gallbladder ejection fraction (EF) was calculated for each dose using the Tc‐99m‐IDA counts to represent the gallbladder bile volume. The mean ejection fraction following 1,2.5,5, and 10 ng/kg given sequentially on the same day was 10 ± 8,22 ± 12,53 ± 13, and 85 ± 3 per cent, respectively. The ejection fraction for 2.5,5, and 10 ng/kg given on separate days was 29.7, 57.14, and 93.3 per cent, respectively, and was similar to the values obtained when the identical dose was given sequentially on the same day (P<0.05). It is concluded that the sequential method is as accurate as the single‐dose regimen and carries the advantages of simplicity in the establishment of dose‐response curve for any future

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb02769.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:Sixty volunteers were endoscopically evaluated to compare gastric mucosal injury following oral administration of sulindac, naproxen, aspirin, or placebo for two consecutive seven‐day periods. A single‐blind technique was utilized wherein the endoscopist was unaware which drug each volunteer had received. The following dosages were employed for the two study periods: sulindac, 150 and 200 mg, b.i.d., naproxen, 250 and 375 mg, b.i.d., and aspirin, 650 and 975 mg, q.i.d. The only subject who developed a frank ulcer with mucosal bleeding was in the sulindac group, however volunteers taking sulindac demonstrated statistically less significant mucosal injury on endoscopic examination than those receiving naproxen or aspi

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb02770.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:Codeine, a relatively weak oral narcotic agent, is the most frequently prescribed oral opiate drug. It is also frequently utilized as a control drug in comparative analgesic efficacy studies. These studies are often single dose analysis of pain relief following surgery or childbirth. We conducted a single dose, post‐operative analysis of 116 patients who were randomly assigned to receive codeine 60 mg, acetaminophen 600 mg, the combination of codeine and acetaminophen at these doses, or a placebo. Only the combination agent was uniformly superior to placebo. Codeine 60 mg was not consistently superior to placebo in this post‐operative single dose analysis. A review of the literature confirms the difficulty in unequivocally establishing the value of codeine as an analgesic, in acceptable oral doses, in the single dose setting. Previous reports, however, suggest that the multiple doses of codeine may afford adequate analgesia. Interpretation of single dose studies with extrapolation to repeated dosing in the practice setting is diffic

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb02771.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:Labetalol, an agent with both alpha‐ and beta‐adrenoreceptor blocking properties, and the beta blocker propranolol were each given for one month to groups of 15 patients with essential hypertension. With either treatment, 11 of the 15 patients experienced decreased supine diastolic blood pressure to less than 90 mm Hg without evidence of fluid retention. Propranolol significantly increased plasma concentrations of uric acid and potassium, whereas labetalol significantly increased plasma concentrations of high‐density lipoproteins (HDL) and decreased the total cholesterol:HDL ratio; neither drug significantly changed renal function. During three additional months of labetalol treatment, there was a slight tendency to orthostatic decreases in systolic blood pressure as compared with the values after the initial month. Labetalol had variable effects on plasma renin activity and aldosterone excretion, but within individual patients the values were constant; there were close correlations between changes measured after one month and after four months for both renin (r= 0.86) and aldosterone (r= 0.94). The manifestations of labetalol's alpha‐blocking component appeared to be a small postural effect on systolic blood pressure and an increase in pla

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb02772.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:Alprazolam, a triazolobenzodiazepine, was administered to 17 patients with alcoholic liver disease. The pharmacokinetic parameters derived from plasma alprazolam concentrations were compared with data obtained from 17 normal subjects who were matched for age and sex. The rate of absorption of alprazolam was slower in patients with alcoholic liver disease. The time of maximum serum concentration was 3.3 hours, compared with 1.5 hour in normals (P<0.02). The maximum concentrations, however, did not differ (18.4 vs. 17.2 μg/ml). The elimination half‐life of drug was longer in the patients (19.7 hours) than in the normal subjects (11.4 hours), while the clearance of the drug was slower in the patients with alcoholic liver disease (0.6 vs. 1.2 ml/min/kg). The volumes of distribution (area) did not differ between the two groups (1.1 vs. 1.2 liter/kg). The changes in elimination half‐life and clearance indicate that the metabolism of the drug is slowed in patients with alcoholic liver dis

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb02773.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:The concentration of caffeine in the blood and semen of men was measured after an oral dose of 200 or 400 mg caffeine. Caffeine was rapidly absorbed (mean tmax= 0.76 ± 0.12 hour), with an average maximum concentration in the blood of 7.4 μg/ml for the 400‐mg dose and 3.4 μg/ml for the 200‐mg dose. The mean clearance of caffeine was 161 and 156 ml/min, while the mean volume of distribution was 50 and 47 liters for the 400‐ and 200‐mg doses, respectively. Distribution of caffeine into the semen was rapid, with a concentration of caffeine in the semen almost identical to that observed concurrently in the blood (blood/semen concentration ratio = 0.97). The mean half‐life of caffeine in the blood and semen was 3.7 and 3.6 hours, respectively, indicating that the decline of caffeine in the blood is very similar to that in semen. Thus, caffeine partitions rapidly into and out of the prostatic and seminal vesicular secretions, which contribute to the formation of t

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb02774.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:Following treatment with cibenzoline, a new antiarrhythmic agent, 23 of 53 patients showed positive proteinuria reactions. In all cases, these results were obtained with bromphenol reagent strips. Subsequent exposure of serial dilutions of cibenzoline to these reagent strips showed positive protein reactions at concentrations as low as 1 mg/ml. Treatment of these same solutions with acetic acid‐sodium acetate heat coagulation technique produced negative findings. Specimens from 14 of the above patients were then retested employing both techniques, and in all cases the reagent strips produced positive results while the heat coagulation technique (or sulfosalicylic acid) produced negative results. Therefore, it appears that cibenzoline produces false‐positive proteinuria results when bromphenol reagent strips are employed for analy

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb02775.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY