The excretion of catecholamines and the changes in plasma concentration of free fatty acids during aminophylline administration were explored. The relationships between cardiac arrhythmia, cardiac rate, and change in blood pressure under the conditions of these experiments were defined. Eighteen experiments were performed on eight volunteers. Blood pressures and heart rates before and during aminophylline infusion were recorded at frequent intervals, and urine and blood were collected during the control and infusion periods and in some subjects after the infusion. Loading with ethanol, glucose, or placebo before administration of aminophylline was used.
These studies demonstrated that intravenous infusion of aminophylline increases the urinary excretion of epinephrine and norepinephrine in man, the rate of excretion of epinephrine being greater than that of norepinephrine. This increase was accompanied by an increase in the concentration of free fatty acids in the plasma.
The excretion of cefazolin, a new cephalosporin antibiotic, was studied in subjects with normal and impaired renal function. Twelve subjects with creatinine clearances ranging from 0 to 144 ml per min per 1.73 m2 were given a single 500-mg intramuscular dose of cefazolin. Serum and urine levels were determined at intervals by agar diffusion. Peak serum levels in normals ranged from 44 to 70 ,ug/ml and occurred 30 to 60 min after injection. The mean serum half-life in normals was 1.6 h, and this was prolonged from 20 to 40% by simultaneous administration of probenecid. The total elimination constant varied linearly with the creatinine clearance in patients with renal impairment. The serum half-life in anephric patients was about 42 h. The fractional clearance of the drug varied directly with the serum level. Peak urine levels ranged from 60 to over 2,000 ,ug/ml, and more than 90% of the dose was recovered in the urine of normals during the first 24 h. The data suggest that cefazolin is cleared primarily by the glomerulus, with tubular and biliary secretion playing a secondary role.
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