摘要:

Abstract:Amrinone was administered orally as a single 100‐mg dose to six male patients with moderate‐severe congestive heart failure to determine the acute pharmacodynamic effects and pharmacokinetics of the drug. Following right heart catherization and amrinone administration, measurements of hemodynamic parameters including cardiac index (CI), right atrial pressure (RA), pulmonary capillary wedge pressure (PCW), and serum amrinone concentrations (SAC) were made at hourly intervals for up to 8 hours. CI increased (29.0 per cent) significantly (P<0.05) at 3 hours after dose. PCW declined quickly after dose and was significantly (P<0.05) lower (–31.3 per cent) than control at 3 hours. RA declined gradually, and a significant (P<0.05) reduction (–25.2 per cent) was achieved 5 hours after the dose. Amrinone was absorbed quickly (tmax= 1.4 hour), and the disappearance of amrinone from serum was log‐linear (t½= 5.1 hours). The time courses of per cent change in CI and SAC were similar, and the correlation between the average per cent change in CI and average SAC was linear and significant (r= 0.

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02631.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:To examine the efficacy of chronic amrinone therapy, the drug was administered to 12 patients with advanced congestive heart failure on average for 27.9 days. The majority of patients had a persistent increase in cardiac index and a persistent decrease in systemic vascular resistance. A decrease in pulmonary arterial diastolic pressure was observed after oral amrinone administration in three patients. However, changes in pulmonary arterial pressure were not consistent in response to intravenous administration of the drug. Thrombocytopenia occurred in four patients, hypogeusia was noted by three patients, and dysosmia developed in two patients. The cumulative survival of the amrinone patients was significantly poorer than that of a second group of patients with congestive heart failure having similar symptoms. These findings indicate that there is a subset of patients with congestive heart failure who do not benefit from chronic amrinone administration and that in such patients its use (especially when given concomitantly with potentially toxic and hypotentsive drugs) should be extremely guarded.

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02632.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:As an introduction into a clinical study of one of a new group of compounds having neuroleptic potential, the background and characteristics of the gamma carbolines, particularly flutroline, are cited in the general context of a review of the use of antipsychotic drugs in psychiatry. In the four‐week double‐blind trial involving dosages of 1, 5, 10, 20 and 100 mg, 48 hospitalized schizophrenic patients were given the tryptoline derivative flutroline on a once‐a‐day basis. Outcome criteria obtained weekly, including the incidence of side effects, standardized psychiatric ratings, and clinical global impressions of psychopathology, indicated that flutroline was a safe and effective antipsychotic drug. Data suggested that dosages of 20 mg and above offered the best potential for optimal clinical effect

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02633.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:Nine patients with resistant hypertension received captopril for 12 months. Five received captopril alone, four required additional therapy. In the former, mean blood pressure fell from 109 ± 4.2 mm Hg to 84 ± 7.5 mm Hg (P<0.025) after seven days. A rise to 101 ± 19 mm Hg was noted at six and 12 months. Total peripheral resistance fell at seven days but returned to levels above control at six and 12 months. Cardiac index was 3.21 ± 0.55 liters/min/m2before treatment, 3.27 ± 0.56 liters/min/m2at seven days, and 2.17 ± 4.0 liters/min/m2(P<0.025) at 12 months. However, forearm blood flow rose from subnormal levels during the 12 months of observation, suggesting a persistent effect on the arterioles of the extremities. Plasma converting enzyme activity was significantly reduced at seven days but was above control levels at six and 12 months. However, plasma renin activity remained elevated, and plasma aldosterone concentration was significantly reduced. The fall in mean blood pressure was not related to the change in plasma converting enzyme activity in patients receiving captopril alone (five patients) or with diuretic (two patients). In the presence of beta‐adrenergic blockade and volume depletion (two patients), changes in mean blood pressure appeared to be related to changes in converting enzyme activity. The data suggest that patients with essential hypertension whose blood pressure was not adequately controlled by previous medications may initially respond to captopril with a fall in blood pressure and total peripheral resistance. However, in certain individuals, these effects diminish with time despite addition of diuretics and beta‐adrenergic receptor blocki

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02634.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:Ciramadol, 20, 40, or 60 mg, or a placebo was administered orally, double blind, to patients complaining of moderate (N= 89) or severe (N= 80) postoperative pain to determine the lowest effective dose. The highest dose used for moderate pain, 40 mg, was statistically more effective than placebo as measured by pain intensity differences and pain relief scores. The highest dose used to treat severe pain, 60 mg, was also more effective statistically than placebo and the lower doses of ciramadol at certain points during the 6‐hour observation period. Drowsiness was minimal, and side effects were infrequent and mild in intensity. We conclude that 40 mg ciramadol for moderate postoperative pain and 60 mg ciramadol for severe postoperative pain would be the minimal oral doses to compare with standard analgesics in future studie

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02635.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:The intraerythrocyte calcium concentration in blood samples of 42 hospitalized alcoholic subjects was initially elevated but declined over a period of several weeks toward normal values. The abnormally high values, which appear to be a direct consequence of prior alcohol ingestion, may explain previous reports of lowered erythrocyte potassium in chronic alcoholics, since there is a specific calcium‐gated potassium channel in erythrocyte membrane

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02636.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:Five healthy male human subjects were administered 200 mg oral solution doses of zomepirac‐14C sodium. Plasma and urine samples were analyzed for zomepirac, hydroxyzomepirac, and zomepirac glucuronide. Zomepirac was the major circulating compound, with zomepirac glucuronide and hydroxyzomepirac accounting for the remainder of the radioactivity. Elimination half‐lives for zomepirac, zomepirac glucuronide, and hydroxyzomepirac were 7.6, 8.2, and 7.8 hours, respectively. The dose was completely recovered in the urine (95 per cent in 72 hours). Zomepirac glucuronide constituted up to 90 per cent of the urinary radioactivity, with zomepirac and hydroxyzomepirac about 5 per cent each. The urinary zomepirac was probably present as a result of hydrolysis of zomepirac glucuronide. The plasma clearance of zomepirac was 189 ± 23 ml/min. The metabolites were cleared by the kidney at rates of 343 ± 88 ml/min (zomepirac glucuronide) and 339 ± 88 ml/min (hydroxyzomepirac). Thus, metabolic clearance appears to be the sole mode of zomepirac elimination. The metabolites are then rapidly cleared by the k

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02637.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:The pharmacokinetics of atropine (dl‐hyoscyamine) was studied in six normal volunteers following a single 1‐mg intravenous dose of atropine. Atropine plasma levels were collected for 24 hours and analyzed by radioimmunoassay. Pulse rates were monitored and compared with predose values in each subject. Atropine plasma concentrations were fitted by least‐squares regression analysis. The observed maximal increase in pulse rate, at 12 to 16 minutes after the dose, correlated with the maximum predicted tissue levels of atropine based on the computer fit of the plasma atropine concentration‐time data. No correlation between the time of maximum response and atropine plasma concentrations was observed. The average half‐life of atropine was 4.125 hours. This data may be used to design a multiple‐dosing regimen for intravenous atropine

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02638.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:Five normal male volunteers participated in an open crossover study designed to examine the disposition of nafcillin given intravenously with and without probenecid. Each subject received two 500 mg iv doses of sodium nafcillin seven days apart, one dose without probenecid and another dose during oral probenecid administration of 1.0 Gm at bedtime prior to the study day and 1.0 Gm two hours before the nafcillin dose. Blood and urine samples were collected for 10 hours after nafcillin dosing. Assay for nafcillin concentrations was performed via the cup‐plate technique withM. Iuteus. Administration of probenecid significantly increased and prolonged circulating plasma concentrations of nafcillin. Probenecid administration significantly, decreased the per cent of nafcillin recovered in the urine (30% vs. 16.9%). Probenecid pretreatment increased the ana under the plasma drug concentration‐time curve (AUC) two‐fold and decreased the total body clearance significantly with decreases in both renal and non‐renal clearance. K12/k21and Vcdid not significantly change with probenecid. Because probenecid coadministration did not appear to change nafcillin distribution while increasing and prolonging plasma concentrations, probenecid can be recommended to be given concurrently when high nafcillin plasma concentrations are desirable. Changes in plasma concentrations are apparently due to alterations in both renal and non‐renal clearances of

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02639.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:Plasma levels of active naphthyridine were measured in healthy old (mean age 77.3 years) and young (mean age 25.4 years) subjects following oral administration of 1 Gm nalidixic acid. The plasma levels of active naphthyridine, i.e., nalidixic acid and its metabolite 7‐hydroxynalidixic acid, were generally higher in the old group, particularly in the elimination phase. Significant variations in the pharmacokinetic parameters were obtained between the two groups of volunteers. The plasma half‐life of active naphthyridine averaged 11.5 hours in old subjects and 2.7 hours in the younger group. Diminished renal function in the geriatric group may explain the slower elimination of the drug in the old subjects. The mean values of the other parameters calculated were: apparent volume of distribution, 0.55 (old) and 0.47 (young) liter/kg body weight; area under the curve, 327.7 (old) and 156.3 (young) μg/ml · hr; total body clearance 2.9 (old) and 8.3 (young) liters/hr; absorption rate constant, 0.29 (old) and 0.52 (young)

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02640.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY