摘要:

Abstract:The central analgesic activity of zomepirac was studied in six healthy subjects by means of intraneural electrical stimulation. Pain elicited by selective activation of nociceptive fibers was inhibited by the administration of a single oral dose of 100 mg zomepirac. Pain relief in this double‐blind crossover study was significantly greater after zomepirac than after placebo. Maximal analgesic effect was observed between 30 and 90 minutes after ingestion. Since peripheral receptors are bypassed by this technique, it is postulated that the observed effect reflects a central action of zomepirac, possibly as a result of inhibition of prostaglandin systhesis in the central nervous syste

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb01815.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:Studies were carried out in 15 patients with renal insufficiency and hypertension to compare the long‐term effects of methyldopa and propranolol on renal hemodynamics. Inulin and PAH clearance measurements were made under baseline conditions and four to six months of antihypertensive therapy with each of the two drugs. Eight of the 15 patients (group I) were started on methyldopa and then switched to propranolol; and in the other seven (group II), the sequence was reversed. There were no statistical differences in blood pressure or inulin or PAH clearances under baseline conditions between the two groups of patients. Blood pressure was controlled equally with the two drugs in combination with furosemide. In group I, there was no significant effect of either antihypertensive drug on inulin clearance, but PAH clearance was significantly higher during methyldopa than propranolol therapy. In group II, the same higher PAH clearance was found with methyldopa, even though the sequence of drug administration was opposite to that of group I. Challenge with iv furosemide resulted in a greater 3‐hour natriuresis during methyldopa than propranolol treatment. The observations indicate that glomerular filtration rate (GFR) is not significantly affected by long‐term treatment with methyldopa or propranolol but that renal plasma flow (RPF) is higher during treatment with methyldopa in patients with renal insufficiency and hypertension. The higher RPF apparently enhances the acute natriuretic effect of iv furos

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb01816.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:Twelve healthy volunteers received a single 40‐mg oral dose of the benzodiazepine derivative oxazolam, which serves primarily as a precursor of the active substance desmethyldiazepam (DMDZ). Concentrations of DMDZ were measured in multiple serum samples drawn for up to two weeks after the dose. Peak serum DMDZ concentrations averaged 115 ng/ml, measured at 8.6 hours after dosage. Mean DMDZ elimination half‐life averaged 61 hours. Three of the subjects also received 40 mg each of prazepam and clorazepate, two other DMDZ precursors, on separate occasions. Although DMDZ elimination half‐life was similar, total area under the curve (AUC) for DMDZ was larger for clorazepate, known to be completely transformed into DMDZ, than for oxazolam or prazepam the extent of whose conversion to DMDZ has not been previously established. After correcting for the different molar equivalent of DMDZ available from each preparation, the DMDZ ratio averaged 0.22 for oxazolam vs. clorazepate and 0.51 for prazepam vs. clorazepate. Thus, both oxazolam and prazepam lead to slow appearance of DMDZ in the systemic circulation. Furthermore the extent of DMDZ formation from oxazolam and prazepam is either incomplete or the drugs are incompletely absorbed. Equivalent doses of oxazolam, prazepam, and clorazepate should not be interchanged in clinical pra

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb01817.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:Clavulanic acid is a β‐lactamase inhibitor which prevents microbial lactamase inactivation of β‐lactam antibiotics. The pharmacokinetics and urinary excretion of clavulanic acid were studied in eight healthy adult volunteers after oral administration of 500 mg amoxicillin and 125 mg potassium clavulanate. Serum and urine clavulanic acid concentrations were assayed using high‐performance liquid chromatography. Pharmacokinetic parameters were: t1/2β = 1.019 ± 0.090 hour, t1/2α = 0.276 ± 0.031 hour, lag time = 0.321 ± 0.018 hour, tmax= 1.042 ± 0.80 hour, Cmax= 2.098 ± 0.441 μg/ml, and AUC = 4.897 ± 0.979 μg · hr/ml. Cumulative urinary excretion of clavulanic acid (as percentage of dose administered) was: 14.05 ± 2.87 within 2 hours, 25.77 ± 3.98 within 4 hours, and 27.85 ± 4.27 within 6 hours

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb01818.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:Previous metabolic studies have established that two major metabolites, 2‐oxoquazepam and N‐desalkyl‐2‐oxoquazepam, are present in plasma after dosing with quazepam, a new benzodiazepine hypnotic. The excretion of quazepam, 2‐oxoquazepam, and N‐desalkyl‐2‐oxoquazepam into human breast milk was studied in four lactating nonpregnant volunteers. Each volunteer received one 15‐mg quazepam tablet following an overnight fast. Nursing of offspring was discontinued after drug administration. Milk and blood samples were collected prior to and at specified times (up to 48 hours) after dosing. Plasma and milk levels of quazepam, 2‐oxoquazepam, and N‐desalkyl‐2‐oxoquazepam were determined by specific GLC methods. The concentrations of the three compounds found in milk appeared to depend on their relative lipophilicities, which were determined by logPvalues. The mean milk/plasma AUC ratios of quazepam, 2‐oxoquazepam, and N‐desalkyl‐2‐oxoquazepam were 4.19, 2.02, and 0.091, respectively. Levels of quazepam and 2‐oxoquazepam declined at about the same rate in plasma and in milk. The total amount of the administered quazepam dose found in the milk as quazepam, 2‐oxoquazepam, and N‐desalkyl‐2‐oxoquaze

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb01819.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb01820.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:The electrophysiologic effects of cibenzoline were studied using programmed electrical stimulation (PES) techniques and were compared to those of quinidine. Cibenzoline, like the conventional class 1 agent quinidine, was effective in preventing arrhythmia induction. Twelve dogs were given 0.02 mg/kg digoxin intravenously for seven days to achieve a steady‐state digoxin level. On the eighth day, cibenzoline was administered in incremental doses (0.5 to 10.5 mg/kg) and PES was performed at 30‐minute intervals. A mean dose of 2.6 ± 0.8 mg/kg cibenzoline prevented ventricular tachycardia induction. At this dose, cibenzoline had no significant effect on mean arterial blood pressure, but PR interval increased by 17 ± 9 per cent, QRS duration by 27 ± 14 per cent, and the ventricular refractory period (ERP) for the first extra stimulus increased by 35 ± 9 per cent. A gradual decrease in heart rate and an increase in PR interval and QRS duration was caused by incremental doses of cibenzoline. In six additional animals, quinidine was administered in incremental doses (1 to 30 mg/kg) and PES performed at 30‐minute intervals. A mean of 15 ± 5 mg/kg prevented induction of ventricular tachycardia in five animals. No significant change in heart rate, PR, QRS, and ERP was found at the effe

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb01821.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY