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1.
In a cross-over study in ten healthy volunteers the effect of food on the absorption of bismuth following a single oral dose of 1200 mg (= 12 Bismofalk tablets) was evaluated by measuring its serum levels (0 to 24 h) and urinary excretion (for seven days). If this high dose was ingested one hour prior to the breakfast maximal serum concentrations (16.5 +/- 13.7 micrograms/l; mean +/- SD) were rapidly achieved (tmax = 0.7 +/- 0.5 h). These levels and the low urinary recovery of 0.32 +/- 0.25 mg (corresponding to 0.027% of the dose) indicated a minimal absorption. If the tablets were taken one hour after the breakfast absorption was slightly delayed (tmax = 1.9 +/- 2.4 h), however, the extent appeared to be unchanged. In spite of the high dosage as well as the large interindividual variability in the urinary recovery and the serum concentrations potential "toxic" serum levels of 100 micrograms/l were never reached. Thus, it can be concluded that the bismuth preparation used is suitable for topical action.  相似文献   

2.
The effect of cefuroxime axetil on the faecal flora of healthy volunteers   总被引:1,自引:0,他引:1  
The effect on the faecal flora of cefuroxime axetil, an oral ester of cefuroxime, was examined in ten healthy volunteers following a dose of 250 mg twice a day for 41/2 days. The mean blood concentration 2 h after the ninth dose was 3.6 mg/l and the urinary excretion was approximately 40% in 6 h and 50% in 24 h. Two volunteers developed mild diarrhoea and one candida vaginitis. Although there was variation between volunteers in the changes found in the faecal flora, the major effects were a reduction in the total anaerobic bacterial count, particularly where high levels of cefuroxime were present in the faeces and a significant decrease or elimination of strains of Enterobacteriaceae plus an increase in the streptococcal count. Six volunteers showed an increase in the candida count. Clostridium difficile was not isolated from any volunteer and toxin was not present in the two volunteers who developed diarrhoea. Four volunteers showed high levels of cefuroxime in the faeces on the fourth or fifth days of treatment.  相似文献   

3.
The pharmacokinetics of fosmidomycin was investigated in animals and humans after parenteral and oral dosing. In dogs the serum concentration was 54.8 microgram/ml at 0.25 h after an intravenous dose of 20 mg/kg, and the half-life was 1.14 h. Peak concentration was 41.4 microgram/ml after an intramuscular dose of 20 mg/kg and 16.6 microgram/ml after an oral dose of 40 mg/kg. In volunteers, the serum concentrations 0.25 h after dosing was 157 microgram/ml after an intravenous dose of 30 mg/kg, 12.3 microgram/ml after an intramuscular dose of 7.5 mg/kg, and 2.45 microgram/ml after an oral dose of 500 mg. More than 90% of the given dose was excreted in the 24-h urine in rats and dogs after parenteral dosing with 20 mg/kg. The 24-h urinary recovery was 45.8% of the given dose in rats after oral dosing with 100 mg/kg and 37.8% in dogs after oral dosing with 40 mg/kg. In volunteers 85.5% of the intravenous dose (30 mg/kg), 66.4% of the intramuscular dose (7.5 mg/kg), and 26.0% of the oral dose (500 mg) were excreted unchanged in the 24-h urine. In the multiple-dose study, there was no accumulation of fosmidomycin in the serum even after 21 consecutive intramuscular dosings of 1 g every 6 h or 29 consecutive 0.5-h drip infusions of 2 g every 6 h. Biliary excretion was extremely low in rats. Fosmidomycin was well distributed to the tissues of rats after parenteral and oral dosing. The lymph concentrations in dogs were nearly the same as serum concentrations. Serum protein binding was low (4% or less) to mouse, rat, dog, and human serum.  相似文献   

4.
The beta-adrenoceptor blocking and diuretic properties of tienoxolol (150 mg and 300 mg) were investigated and compared to those of a placebo in a double-blind, cross-over trial in six healthy volunteers. Heart rate (HR), systolic and diastolic blood pressures, peak expiratory flow rate (PEFR) at rest and during vigorous exercise, plasma renin activity (PRA) and aldosterone levels at rest, and diuresis and urinary electrolyte excretion values were measured before and at intervals up to 24 h after oral administration of the drugs. In addition, the clearances of electrolytes, uric acid, and creatinine were calculated, as well as the fractional sodium excretion (Fe Na%) before and 4 h and 24 h after drug intake. Finally, tienoxolol plasma levels were measured. Tienoxolol significantly and dose-dependently reduced exercise-induced tachycardia. This effect started 1 h after drug administration, peaked between 4 h and 6 h (-12% and -17% from control values at 150 mg and 300 mg, respectively), and lasted at least 12 h. Resting HR was decreased at 300 mg (P less than 0.05), PRA was decreased at both doses (P less than 0.05), but PEFR was not drug-affected. 24-h cumulative sodium excretion was increased (+24% at 150 mg [NS], +38% at 300 mg [P less than 0.01]) as compared to placebo, and Fe Na% did not change, regardless of the dose administered. 24-h cumulative diuresis was moderately increased by tienoxolol (NS), whereas creatinine clearance rose after the 300-mg dose, suggesting that tienoxolol might increase glomerular filtration rate. Plasma aldosterone levels remained unchanged. Finally, the elimination half-life of tienoxolol was 7.5 h. Thus, in healthy volunteers, tienoxolol behaves as an early acting and relatively long-lasting selective beta 1-adrenoceptor blocking drug endowed with significant natriuretic properties.  相似文献   

5.
A 12-year-old Japanese boy was referred to our hospital with a 2-month history of persistent proteinuria. Despite urinary protein excretion in the nephrotic range, associated with hypoproteinemia, the patient did not complain of any disability. A percutaneous renal biopsy revealed minor glomerular abnormalities, without any evidence of immune complex deposition. Therapy with prednisolone (60 mg/day) was initiated, and while the proteinuria decreased after 4-week therapy, elevated urinary protein excretion persisted thereafter, at 1-2 g/day. Because of the steroid-resistant proteinuria, mizoribine (MZR), was started at 150 mg/day (3 mg/kg), administered as a single daily dose an immunosuppressive agent, in combination with prednisolone. Although there was some fluctuation in the urinary protein excretion, heavy proteinuria persisted for the next 4 weeks. The peak blood level of MZR was 0.9 microg/ml. Since we have previously reported the efficacy and safety of oral MZR pulse therapy, which is associated with higher peak serum MZR levels than conventional MZR therapy in selected patients with lupus nephritis, we adopted MZR pulse therapy for this patient, after obtaining informed consent. MZR was started at the daily dose of 300 mg (6 mg/kg), administered as a single dose before breakfast, twice a week (on Monday and Thursday). The peak blood level of MZR then increased to 1.29 microg/ml. Thereafter, despite a gradual reduction of the concomitantly administered prednisolone dose, the urinary protein excretion decreased rapidly to around 0.3 g/day and remained at this level thereafter. No adverse effects of MZR were observed. Based on these clinical observations, we suggest that oral MZR pulse therapy may be the treatment of choice in selected patients of steroid-resistant nephrotic syndrome, in addition to those of lupus nephritis.  相似文献   

6.
Eight healthy men received single oral doses of 400, 800, and 1200 mg medroxalol and a single intravenous dose of 1 mg per kg body weight on four occasions separated by at least 2 wk. Plasma medroxalol concentrations were assayed up to 24 hr after each dose by a specific high-pressure liquid chromatographic assay. Urinary excretion of parent compound was determined as well. Following oral doses medroxalol reached peak plasma concentrations within 2.5 to 3 hr. The t 1/2 of the terminal decay phase was 11.1 hr. Mean apparent volume of distribution (aVD) was between 11.2 and 16.4 l/kg, and mean total body clearance (ClT) was between 0.73 and 0.99 l hr-1 kg-1. Mean urinary recovery of parent drug within 48 hr was 2.3%, 3.9%, and 3.6% after the oral doses compared to 8.2% after the intravenous dose. Bioavailability estimated from AUC was 27.2% after 400 mg, 31.3% after 800 mg, and 37.4% after 1200 mg by mouth. Since aVD, t 1/2, ClT, and urinary excretion did not differ significantly after the three oral doses, medroxalol kinetics appear to follow a dose-linear model.  相似文献   

7.
Following intravenous infusion of 800 mg of 14C-tinidazole during 30 min to two human subjects, a mean of 44% of the dose was excreted in urine during the first 24 h, increasing to 63% of the dose during five days: 12% of the dose was excreted in the faeces, indicating the possible involvement of biliary excretion and other secretory processes in the disposition of tinidazole. At 6 min after the end of the infusion, the mean plasma tinidazole concentration was 12 mg/l. Tinidazole was a major component in 0-120 h urine (about 32% of urinary 14C): the major metabolite in the 0-12 h urine examined was ethyl 2-(5-hydroxy-2-methyl-4-nitro-1-imidazolyl)ethyl sulphone (about 30% urinary 14C), the product of hydroxylation and nitro-group migration. These compounds were also present in the faeces. A minor urinary metabolite was 2-hydroxymethyltinidazole (about 9% urinary 14C), which was also present in plasma. The mean pharmacokinetic parameters obtained for tinidazole were similar to those reported in the literature; total clearance 51 ml/min, renal clearance 10 ml/min, volume of distribution 501 and half-life 11.6 h.  相似文献   

8.
Effects of carbidopa, a dopa (3,4-dihydroxyphenylamine) decarboxylase inhibitor, on the renal, haemodynamic and hormonal responses to acute volume expansion were examined in six healthy mongrel dogs which were infused intravenously with 0.9% sodium chloride solution (saline; 30 ml h-1 kg-1) over 2 h. Saline infusion studies were performed in the absence (control) and in the presence of carbidopa given by nasogastric tube in a dose of 1 mg/kg every 8 h beginning 24 h before the infusion. Saline infusion resulted in an increase in renal excretion of dopamine (3,4-dihydroxyphenylethylamine) and a decrease in renal excretion of noradrenaline. Carbidopa treatment decreased urinary sodium excretion and eliminated the increase in renal production of dopamine in response to saline infusion without affecting renal or haemodynamic response to acute vascular volume expansion with saline. Carbidopa treatment obliterated the suppression of aldosterone produced by saline infusion. Thus, dopamine appears to play a significant role in mediating both the natriuretic and aldosterone response to acute volume expansion.  相似文献   

9.
Cefixime, in-vitro activity, pharmacokinetics and tissue penetration   总被引:4,自引:0,他引:4  
The in-vitro activity of cefixime was studied with clinical isolates and compared with that of other agents. Cefixime exhibited good activity against the Enterobacteriaceae, Haemophilus influenzae, and Neisseria gonorrhoeae, including beta-lactamase producing strains. Activity was also high against Streptococcus pneumoniae and group A and group B beta-haemolytic streptococci. Staphylococcus aureus, faecal streptococci, anaerobic bacteria and Pseudomonas aeruginosa were not susceptible. Activity against susceptible isolates was comparable to cefotaxime and was normally superior to cefuroxime, cephalexin and amoxycillin. The pharmacokinetics of cefixime were studied in six healthy male volunteers, each receiving a 400 mg oral dose following an overnight fast. Tissue penetration of the antibiotic was estimated with a cantharides-induced blister method. The mean serum elimination half-life was 3.8 h, the mean peak concentration was 3.7 mg/l. Penetration into tissue fluid was rather slow [Tmax 6.7 h) but percentage penetration was high (132.6%). Urinary excretion was low with a 24 h recovery rate of less than 20%, though the concentrations achieved in urine exceeded the MICs of most common urinary tract pathogens for up to 24 h post-dose.  相似文献   

10.
A cross-over study was performed comparing serum kinetics and urinary excretion in six healthy, fasting volunteers after ingestion of comparable amounts of lenampicillin, bacampicillin and amoxycillin. Venous blood samples and urine samples were taken at intervals for 6 and 12 h respectively post-tablet ingestion and assayed for free ampicillin or amoxycillin concentration with Bacillus subtilis as indicator organism. The most rapid Tmax and the highest Cmax were achieved with lenampicillin. The AUC was similar for lenampicillin, bacampicillin and amoxycillin as was the total percentage urinary recovery of antibiotic. Potential pharmacokinetic advantage of orally administered lenampicillin and bacampicillin compared to comparable doses of amoxycillin are higher peak serum concentrations (12.0 mg/l lenampicillin; 9.7 mg/l bacampicillin; 7.6 mg/l amoxycillin) and more rapid time to peak concentration (0.6 h lenampicillin; 0.7 h bacampicillin and 1.4 h amoxycillin).  相似文献   

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