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Biomedical subjects

G R Aronoff

Publications and source records attributed to G R Aronoff.

90 records · Page 5Linked to original sources
PubMed1982

Mezlocillin dose dependent elimination kinetics in renal impairment.

The effect of drug dose on mezlocillin elimination kinetics was examined in six subjects with normal renal function and in six anuric patients. Each subject received mezlocillin 1,3 and 5 g as single intravenous doses separated by one week. Elimination was not prolonged by increasing the dose in subjects with normal renal function, but elimination kinetics were dose dependent in anuric patients. Therapeutic guidelines are suggested.

Adult↗
PubMed1982

Benoxaprofen kinetics in renal impairment.

To establish therapeutic guidelines, benoxaprofen kinetics were examined in 26 adult subjects with normal and decreased renal function. Mean peak plasma concentrations after a single 600-mg dose ranged from 58 to 72 mg/l, independent of renal function. Elimination half-life and benoxaprofen plasma clearance correlated with creatinine clearance. Hemodialysis did not remove benoxaprofen from plasma. A dosage nomogram was derived from which a dose one half of the normal maintenance dose was suggested for patients with severe renal failure.

Adult↗
PubMed1982

Pharmacokinetics of moxalactam in patients with normal and impaired renal function.

Moxalactam is the first representative of a new class of potent beta-lactam antibiotics. To establish dosage recommendations, the kinetics of moxalactam elimination were studied in 20 patients with various degrees of renal dysfunction. After a 1-g intravenous bolus injection, the elimination half-life increased from 2.2 +/- 0.1 hr in normal subjects to 22.3 +/- 1.7 hr in anuric patients. Similar correlations were shown between the rate of creatinine clearance and the rate of plasma clearance, the rate of renal clearance, and the overall elimination rate constant of moxalactam. No changes in the distribution volumes or metabolic clearance rates of moxalactam were detected. A nomogram for adjustment of moxalactam dosage in patients with any level of renal function was generated, and specific recommendations for moxalactam dosage are discussed.

Adult↗
PubMed1982

Effects of moxalactam and cefotaxime on rabbit renal tissue.

To determine and compare the effects of moxalactam and cefotaxime on kidneys, we gave these drugs in doses of 750 and 1,500 mg/kg to rabbits for 7 days. Cephaloridine was included as a positive control. Neither moxalactam nor cefotaxime at either dose caused lysosomal enzymuria, changes visible by light microscopy or increased plasma creatine. Both drugs caused minor alterations in glomerular ultrastructure at the higher dose. Cephaloridine, on the other hand, caused widespread renal functional and morphological damage. We conclude that in rabbits, both moxalactam and cefotaxime are remarkably nonnephrotoxic.

Acetylglucosaminidase↗
PubMed1982

The renin-angiotensin system in aminoglycoside-induced acute renal failure.

To examine the role of the renin-angiotensin system in aminoglycoside-induced acute renal failure, we gave rats gentamicin (80 mg/kg/day), gentamicin + captopril (an angiotensin-converting enzyme inhibitor), captopril alone or saline sham injections, for 10 days. Blood pressure, sodium excretion, urine osmolality and creatinine clearance were measured four times during treatment. Plasma renin activity, angiotensin I-converting enzyme and renal histology were determined at sacrifice. Although angiotensin I-converting enzyme activity was markedly suppressed by captopril treatment, the addition of captopril failed to consistently influence blood pressure or urine osmolality. In addition, it did not promote natriuresis in the face of gentamicin toxicity. Creatinine clearance decreased progressively in groups receiving gentamicin and was lowest (P less than .05) in the groups receiving gentamicin + captopril. Captopril did not prevent the development of tubular epithelial nor glomerular endothelial changes associated with gentamicin toxicity. In a separate experiment rats received captopril for 3 days prior, before receiving the gentamicin + captopril regimen for 10 days. Captopril pretreatment did not influence the results. This study does not support a pivotal role for the renin-angiotensin system in the production of the decreased glomerular filtration rate observed in nephrotoxic acute renal failure induced by gentamicin in rats.

Acute Kidney Injury↗
PubMed1981

Management of amikacin overdose.

A woman with subarachnoid hemorrhage inadvertently received 18 g of amikacin over a 4-hr period, 20 times the recommended total daily dose. Intravenous fluids were administered to expedite renal excretion of the amikacin, and a peritoneal dialysis was performed to augment drug elimination. Drug levels were measured sequentially in serum, urine, and peritoneal dialysate. Renal clearance of the drug was increased compared to clearance following a standard dose and the drug was rapidly excreted in the urine. Amikacin was not detected in the peritoneal dialysate. There were no apparent toxic effects from the overdose. A patient with normal renal function who receives a potentially toxic dose of amikacin can be appropriately managed by careful hydration and maintenance of a generous diuresis.

Adult↗
PubMed1981

Effects of vancomycin on renal function in rats.

To assess the effects of vancomycin on the kidney, we gave rats doses of 10, 50, 100, 200, and 400 mg/kg per day. Creatinine clearance and urine protein excretion did not differ significantly from the control values. Urine osmolality was unchanged. Mild histological changes occurred in rats given the highest dose. We conclude that although histopathological changes occurred at high doses, vancomycin does not alter renal function in rats.

Animals↗
PubMed1981

Moxalactam pharmacokinetics during hemodialysis.

To establish dosage recommendations, moxalactam elimination kinetics were studied in six anephric patients during hemodialysis and in four anephric patients during the interdialytic period. After a single 1-g intravenous bolus injection, moxalactam elimination half-life was 18.0 plus or minus 0.6 h with a volume of distribution of 20.2 plus or minus 3.6 liters and a plasma clearance of 12.8 plus or minus 2.0 ml/min in four nondialyzed patients. Moxalactam elimination half-life was decreased to 2.7 plus or minus 0.2 h during hemodialysis in six patients. After 4 h, 48.5% of the dose was recovered in the dialysate. The maintenance dose of moxalactam should be decreased to 15% of a normal dose in patients with creatinine clearances less than 10 ml/min, and 50% of a loading dose should be given after hemodialysis.

Aged↗
PubMed1981

Mezlocillin enteral absorption in rabbits.

To determine the role of enterohepatic recirculation on its nonlinear elimination, we studied the enteral absorption of mezlocillin in rabbits. Mezlocillin was not substantially absorbed from the stomach or duodenum. We conclude that enterohepatic recirculation does not cause the dose-dependent elimination kinetics of mezlocillin.

Animals↗
PubMed1981

The effect of aminoglycosides on glomerular endothelium: a comparative study.

In addition to being tubular nephrotoxins, the aminoglycosides are known to injure the glomerular endothelium by decreasing the diameter and density of endothelial fenestrae. To determine whether or not these changes correlate with the rank order of toxicity we compared in rats the effects of netilmicin, tobramycin, and amikacin on renal function, tubular and glomerular ultrastructure, at 10 and 25 times the recommended human dose. According to measurements of glomerular filtration rate their rank order of toxicity, in increasing severity was: netilmicin, tobramycin, and amikacin. The same order of effect was observed on glomerular ultrastructure. Thus glomerular structural changes correspond to glomerular functional changes in this model.

Amikacin↗
PubMed1980

Mezlocillin pharmacokinetics in renal impairment.

Mezlocillin kinetics was examined in 28 adult subjects with varying renal function. Mezlocillin 3 gm, was infused over 30 min. Mean peak plasma concentrations ranged from 204 to 253 mg/I. When the area under the curve (AUC) was plotted against creatinine clearance (CCr), the relationship found was expressed by the equation AUC = 656e(-0.01)(CCr). From this relationship a dosage nonogram was derived describing a power function with the following equaton: Dose fraction = 1.32--e(-0.01)(CCr). Therapeutic guidelines are suggested.

Adult↗
PubMed1980

Hypoxanthine-arabinoside pharmacokinetics after adenine arabinoside administration to a patient with renal failure.

Hypoxanthine arabinoside pharmacokinetics were measured during an adenine arabinoside continuous intravenous infusion and during hemodialysis in a patient with renal failure. Therapeutic guidelines for adenine arabinoside in renal failure are provided based on an elimination half-life of 4.7 h and a plasma clearance of 87.9 ml/min for the hypoxanthine metabolite.

Acute Kidney Injury↗
PubMedDate not supplied

Microbiology, pharmacology, and clinical use of mezlocillin sodium.

The acylureido penicillin mezlocillin is active against gram-positive, gram-negative, and anaerobic bacteria. It easily penetrates the outer membrane of gram-negative bacteria, and it has a strong affinity for penicillin binding protein 3. Its stability to beta-lactamases is weak. Mezlocillin is synergistic when given in combination with aminoglycoside antibiotics. In pharmacokinetic studies mezlocillin conforms to a two compartment open model; its pharmacokinetic properties are dose-dependent. The half-life of the drug is about 1 hour after intravenous injection and 1.5 hours after intramuscular injection. Protein binding ranges from 16 to 42%, and 55% of a dose is excreted in the urine. Biliary excretion ranges from 0.5 to 25%. Clinical trial cure rates were as follows: bacteremia (78%), respiratory tract (62%), urinary tract (81%), gynecological (86%), bone and joint (55%), intraabdominal (67%) and skin and soft tissue (59%). The frequency of adverse reactions was 7.7%. Interstitial nephritis, CNS toxicity, and bleeding have not been reported.

Bacteria↗
PubMedDate not supplied

Increased serum iodide concentration from iodine absorption through wounds treated topically with povidone-iodine.

Increased serum iodide concentrations secondary to iodine absorption through wounds treated with povidone-iodine dressings is described. Hyperchloremic acidosis and a disparity between serum chloride concentrations determined by two different methods suggested the presence of an unidentified halide. Cardiovascular instability and renal failure occurred concurrent with systemic iodide accumulation. Measurement of serum iodide concentration should be performed when povidone-iodine is used topically in patients with impaired renal function.

Aged↗
PubMedDate not supplied

Calcium channel blockade with nitrendipine. Effects on sodium homeostasis, the renin-angiotensin system, and the sympathetic nervous system in humans.

To test the hypothesis that the antihypertensive effect of the calcium channel blocking drug nitrendipine is in part related to natriuresis, we gave 16 subjects (8 normal, 8 hypertensive) placebo for 8 days followed by nitrendipine titrated to 20 mg twice daily for 8 days. The same diet was prepared for each meal for the entire study. Sodium intake was fixed for each subject and averaged 150 mEq/day. All urine was collected every day. Blood was drawn at the end of the placebo and nitrendipine periods for renin, aldosterone, and norepinephrine values. Nitrendipine caused a significant increase (p less than 0.05) in cumulative sodium excretion of 161 mEq over 7 days in the normal subjects and 103 mEq in hypertensive subjects. Potassium excretion was unaffected. In both hypertensive and normal subjects, plasma renin and plasma norepinephrine activity increased significantly (p less than 0.05), while plasma aldosterone levels did not change. Upright systolic blood pressure decreased significantly (p less than 0.05) in both groups, whereas upright diastolic blood pressure decreased only in hypertensive subjects. We conclude that blood pressure lowering effects of this drug may be in part related to natriuresis and that calcium channel blockade may dissociate plasma renin activity from that of aldosterone.

Adult↗