摘要:

Clinical Pharmacology and Therapeutics(1986)39,481–488; doi:10.1038/clpt.1986.

ISSN:0009-9236    

DOI:10.1038/clpt.1986.84

年代:1986

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1986)39,489–490; doi:10.1038/clpt.1986.

ISSN:0009-9236    

DOI:10.1038/clpt.1986.85

年代:1986

数据来源: WILEY

摘要:

The effects of diazepam (0.2 mg/kg for 15 days followed by 0.3 mg/kg for 7 days), oxazepam (0.8 mg/ kg for 15 days followed by 1.2 mg/kg for 7 days), and placebo were studied in healthy subjects after the first dose, once a week during chronic dosing, and at 48 and 96 hours after withdrawal through a battery of psychologic tests. Diazepam produced quick effects followed by relatively rapid recovery, whereas the effects of oxazepam appeared slowly and lasted longer. Tolerance developed to the effects of both active drugs, so that when the dosages were increased, effects did not. There were no symptoms or signs indicative of withdrawal reactions. There were also no differences between the effects of the two active drugs after repeated dosing, although diazepam is an accumulating drug with active metabolites and oxazepam is a slightly accumulating one with inactive metabolites.Clinical Pharmacology and Therapeutics(1986)39,491–500; doi:10.1038/clpt.1986.

ISSN:0009-9236    

DOI:10.1038/clpt.1986.86

年代:1986

数据来源: WILEY

摘要:

We added phenylpropanolamine OROS (Acutrim; Ciba‐Geigy Corp.) or placebo to a physician‐managed behavior modification, mild caloric restriction, and exercise weight control program. One hundred six healthy, overweight (115% to 130% ideal body weight) women participated in this 14‐week double‐blind clinical trial. On average, the participants who took Acutrim lost significantly more weight (X̄ ± SE; 6.1 ± 0.6 kg; 8.0% ± 0.8%) than did those taking placebo (4.3 ± 0.7 kg; 5.5% ± 0.8%; P<0.05). Those taking Acutrim continued to lose weight over the Christmas holiday, while the placebo group gained weight. Fifteen participants taking placebo withdrew, three because of adverse drug reactions (ADRs). Thirteen of 53 participants in the Acutrim group left the study, two because of ADRs. Dry mouth was the most frequent complaint from participants taking Acutrim. No serious cardiovascular effects occurred. Both complaints and the number of participants reporting ADRs decreased with continued dosing. We conclude that Acutrim is a safe, modestly effective adjunct to a physician‐managed, integrated weight control program.Clinical Pharmacology and Therapeutics(1986)39,501–509; doi:10

ISSN:0009-9236    

DOI:10.1038/clpt.1986.87

年代:1986

数据来源: WILEY

摘要:

Tin (Sn4+)‐Protoporphyrin, a potent competitive inhibitor of heme degradation to bile pigment, was cleared rapidly from plasma in normal subjects (t½~4 hours for plasma levels>5 nmol/ml, with evidence of dose‐dependent pharmacokinetics at lower plasma concentrations). Small amounts were excreted promptly in urine (0.1% to 5.6%) and more gradually in feces (3.7% to 11.3%). The only dose‐limiting (>1.0 μmol/kg, single dose) side effect was mild sensitivity to sunlight and long‐wave ultraviolet light. Absorption after intramuscular administration was rapid, but there was no absorption after oral dosing. In bile duct—ligated rats treated with Sn‐protoporphyrin, there was a substantial (approximately 50%) reduction in plasma bilirubin levels compared with levels in ligated control animals. Seven studies were carried out in four women with moderate to severe cholestasis secondary to primary biliary cirrhosis and in two men with Gilbert's syndrome. In these studies Sn‐protoporphyrin (total doses of 0.25 to 2.0 μmol/ kg body weight) reduced plasma bilirubin levels to a varying degree (7% to 43%) promptly after its intravenous administration.Clinical Pharmacology and Therapeutics(1986)39,510–520; doi:1

ISSN:0009-9236    

DOI:10.1038/clpt.1986.88

年代:1986

数据来源: WILEY

摘要:

The effect of diphenhydramine on the cyanamide‐ethanol reaction was evaluated in a double‐blind, controlled clinical study. Seven healthy subjects ingested 50 mg calcium carbimide at 4 hours and 100 mg diphenhydramine or placebo at 2 hours before a 0.2 gm/kg iv infusion of ethanol. Blood acetaldehyde and blood ethanol analyses were performed together with recordings of blood pressure, pulse rate, and flushing intensity during the hour after ethanol infusion. Diphenhydramine increased the mean ethanol AUC but did not influence blood acetaldehyde levels. Antihistamine reduced the flushing response by 40% and decreased the pulse rate from 40 minutes onward after ethanol infusion subsequent to calcium carbamide dosing. Blood pressure was not significantly influenced by ethanol at the calcium carbimide dose we used.Clinical Pharmacology and Therapeutics(1986)39,521–525; doi:10.1038/clpt.1

ISSN:0009-9236    

DOI:10.1038/clpt.1986.89

年代:1986

数据来源: WILEY

摘要:

Seven healthy subjects received oral placebo, 1.5 mg lorazepam, or 3.0 mg lorazepam in a single‐dose, three‐way crossover study. Plasma lorazepam concentrations and subjects' self‐rated sedative effects were evaluated at multiple points during 24 hours after each dose. Information acquisition and recall was studied by use of a 16‐item word list at 3 and 24 hours after dosing. Lorazepam plasma concentrations were proportional to dose. Self‐rated sedation was maximal 2 to 3 hours after lorazepam dosing, persisted for 8 hours, and was dose dependent in intensity; no significant sedation occurred with placebo. At 3 hours after placebo dosing, subjects learned a mean 96% of words presented during six trials; this was reduced to 79% and 62% after lorazepam, 1.5 and 3.0 mg, respectively (F = 6.2; P<0.02). Twenty‐four hours after placebo, subjects recalled 92% of words presented the previous day, then improved to 99% after six relearning trials. After 1.5 and 3.0 mg lorazepam, however, only 52% and 44% of words were initially recalled from the previous day. Thus single oral doses of lorazepam within the therapeutic range produce dose‐dependent sedation and impairment of information acquisition and recall.Clinical Pharmacology and Therapeutics(1986)39,526–530; doi:10.1

ISSN:0009-9236    

DOI:10.1038/clpt.1986.90

年代:1986

数据来源: WILEY

摘要:

We have studied three circumstances that have been reported to make interpretation of the serum digoxin concentration difficult in patients with renal failure: increased biotransformation; endogenous digitalis‐like factors (DLF); and sudden, unexpected increases in serum digoxin values, even after the discontinuation of digoxin. Biotransformation, as estimated by the percent true digoxin in serum, was comparable in patients with renal failure who were dependent on dialysis and in control subjects (76% vs. 73%). Certain commercial immunoassays did not, or rarely, gave values for DLF of clinical significance (>0.2 ng/ml digoxin equivalents) in patients with a wide range of renal dysfunction who were not receiving digoxin. With a sensitive method, values for DLF did not exceed 0.23 ng/ml in 22 dialysis patients dependent on dialysis, but were significantly increased in comparison with values in control subjects. The case histories of two patients with renal failure, acute illness, and sudden unexpected marked increases in serum digoxin concentrations are presented and possible explanations are discussed.Clinical Pharmacology and Therapeutics(1986)39,530–536; doi:10.1038/clpt.198

ISSN:0009-9236    

DOI:10.1038/clpt.1986.91

年代:1986

数据来源: WILEY

摘要:

The efficacy and tolerance of the loop diuretic muzolimine were compared with those of a fixed combination of hydrochlorothiazide and amiloride in patients with mild to moderate hypertension. After a placebo lead‐in period, patients whose supine diastolic blood pressure was between 90 and 115 mm Hg were randomly allocated either to muzolimine, 20 mg/day, or to hydrochlorothiazide, 50 mg/day, and amiloride, 5 mg/day. The mean duration of follow‐up was 4.7 months in both groups. Both muzolimine and the combination significantly decreased the mean blood pressure. The two treatments were similar in efficacy. The incidence of side effects during the trial was similar with both treatments, and no serious adverse reactions occurred. Eleven subjects in the muzolimine group were entered into an open long‐term study. In all these subjects the blood pressure remained adequately controlled throughout the 4 to 6 months of additional follow‐up and no side effects were reported. Muzolimine appears to be an effective and safe antihypertensive agent.Clinical Pharmacology and Therapeutics(1986)39,537–542; doi:10.1038/cl

ISSN:0009-9236    

DOI:10.1038/clpt.1986.92

年代:1986

数据来源: WILEY

摘要:

The tolerance and β‐adrenergic blocking activity of flestolol, a short‐acting β‐blocker, was investigated in 30 subjects. Flestolol infused intravenously at doses up to 100 μg/kg/min was found to be well tolerated. A dose‐dependent attenuation of isoproterenol‐induced tachycardia and increase in systolic blood pressure occurred with flestolol at doses ranging from 0.5 to 15.0 μg/kg/min. The average percent reduction in isoproterenol‐induced tachycardia (β‐blockade) at each dose of flestolol, 0.5, 2.5, 5.0, 15.0, and 50.0 μg/ kg/min, was 15.1%, 45.9%, 67.0%, 85.9%, and 90.3%, respectively. The onset of β‐blockade occurred within 30 minutes. After the end of flestolol infusion there was a marked reduction in β‐blockade within 6 minutes, with complete recovery from β‐blockade within 30 to 45 minutes. There was a statistically significant (P<0.01) positive correlation between flestolol dosage and its blood levels (r = 0.91) as well as between the flestolol‐induced β‐blockade and its dosage (r = 0.62).Clinical Pharmacology and Therapeutics(1986)39

ISSN:0009-9236    

DOI:10.1038/clpt.1986.93

年代:1986

数据来源: WILEY