Interactions between mezlocillin and sisomicin in vitro and in patients with normal and various degrees of impaired renal function.

During in vitro experiments using pooled human plasma at 37 degrees C, sisomicin alone showed only a small loss of activity of 12% in 24 hr. Incubation with 80 micrograms/ml mezlocillin did not alter the rate of inactivation. But, after the addition of 300 micrograms/ml mezlocillin to either 5.0 or 2.5 micrograms/ml sisomicin, the sisomicin half-life was reduced by 50% and 100% respectively. When the mean drug concentration ratios are compared, inactivation of sisomicin by mezlocillin was significantly less than that reported for carbenicillin or ticarcillin. Sisomicin pharmacokinetics were studied in 27 patients with normal and various degrees of impaired renal function (Part A) and were not changed by the simultaneous administration of mezlocillin 60 mg/kg (Part B). Furthermore, even in far advanced renal insufficiency, sisomicin inactivation by mezlocillin could not be demonstrated. The differing results obtained with mezlocillin compared to carbenicillin or ticarcillin might be explained by differences in the physico-chemical properties of the drugs in addition to the different kinetic behavior of mezlocillin in patients with impaired renal function.

[Effect of diffusion potentials and various stomach regions on the behavior of the potential difference after pentagastrin]. / Der Einfluss von Diffusionspotentialen und der verschiedenen Magenregionen auf das Verhalten der Potentialdifferenz unter Pentagastrin.

Junction potentials at the tip of a 0.15 M NaCl- and a 3 M KCl-flowing bridge dependent on the surrounding electrolyte solution were measured and calculated. There was a close correlation between the calculated and measured junction potentials. The magnitude of the calculated and experimentally determined junction potentials at the tip of the 0.15 M NaCl-bridge was found to be almost identical. Provided that junction potentials were not subtracted from the measured potential difference pentagastrin diminished the simultaneous measured antrum and corpus potential difference in 11 volunteers. When however junction potentials from the experimentally determined potential difference had been subtracted pentagastrin induced a transient significant decline in the corpus potential difference but no significant changes of PD could be registered in the antrum. The observation that pentagastrin did not change the antrum-PD suggests that the pentagastrin effect is related to the parietal cells.

Cefoxitin pharmacokinetics: relation to three different renal clearance studies in patients with various degrees of renal insufficiency.

The pharmacokinetics of cefoxitin were examined in 4 healthy volunteers, 6 patients with normal renal function (inulin clearance, greater than 80 ml/min per 1.73 m2), and 35 patients with various degrees of renal insufficiency (inulin clearance, 80 to less than 5 ml/min per 1.73 m2). A single dose of 30 mg of cefoxitin per kg of body weight was injected intravenously over 3 min. Antibiotic concentrations in plasma were determined by the agar diffusion technique. The cefoxitin half-life increased progressively from 39 min in subjects with normal renal function to 23.5 h in oligoanuric patients. Correspondingly, total body clearance decreased from 340 to 13 ml/min per 1.73 m2. In addition to the study of cefoxitin kinetics, in 29 of the 41 patients, three different renal clearance tests were performed (inulin, p-aminohippurate, and creatinine clearances). Of these, p-aminohippurate clearance showed the best correlation with the elimination rate constant beta as well as total body clearance of cefoxitin; but with respect to beta, the differences between the p-aminohippurate and creatinine clearances were quantitatively negligible. Therefore, even in substances which are eliminated predominantly by active tubular secretion, creatinine clearance could be recommended for dosage adjustments.

Outpatient evaluation of dietary intake and nitrogen removal in continuous ambulatory peritoneal dialysis.

Five patients on continuous ambulatory peritoneal dialysis were studied to evaluate dietary intake, glucose absorption from the dialysate, and urinary and dialysate nitrogen removal. The study was done on an outpatient basis, while the patients ingested their usual diets and went about their usual activities. The results indicate that patients greatly overestimated their caloric and protein intake, which was 0.71 to 0.96 g/kg bodyweight per day. Dialysate glucose contributed considerably to total caloric intake, because approximately 75% of of the dialysate glucose was absorbed independent from total glucose administered, providing 20% to 29% of the total caloric intake. We concluded that protein requirement in clinically stable continuous ambulatory peritoneal dialysis patients still needs defining because the patients may be anabolic with lower protein intakes than previously recommended.

Effects of impaired renal function, hemodialysis, and peritoneal dialysis on the pharmacokinetics of mezlocillin.

The pharmacokinetics of mezlocillin were examined in 8 patients with normal renal function (inulin clearance, > 80 ml/min per 1.73 m2), 32 patients with moderately reduced renal function (inulin clearances, 80 to 5 ml/min per 1.73 m2), and 12 patients maintained by hemodialysis or peritoneal dialysis because of severely impaired renal function. A single dose of 60 mg of mezlocillin per kg of body weight was infused intravenously over 30 min. Antibiotic concentrations in plasma, urine, and dialysate were determined by the agar diffusion technique. The half-life of mezlocillin increased with decreasing renal function from an average of 53 min in subjects with normal function to 165 min in oligoanuric patients. The urinary recovery of this drug in 24 h decreased from 65% at a glomerular filtration rate of 92 ml/min to 7.6% at a glomerular filtration rate of 6.7 ml/min. Volume of distribution was not changed by the renal insufficiency, amounting on the average to 22.5% of body weight. Intermittent hemodialysis or peritoneal dialysis contributed to only a minor degree to the 24-h mezlocillin kinetics. The pharmacokinetic properties of mezlocillin permit a normal dosage over wide ranges of renal insufficiency; however, when the glomerular filtration rate is below 10 ml/min, the dosage interval should be increased from 8 to 12 h.

Clinical and metabolic aspects of continuous ambulatory peritoneal dialysis (CAPD).

Experience with CAPD in 14 patients, treated for periods of 2-10 months, is presented. Clinical and biochemical control of uremia appeared adequate in all patients except one. Control of extracellular volume and hypertension was easier with CAPD than with intermittent peritoneal dialysis (IPD). Nine episodes of peritonitis occurred in 5 patients (one peritonitis/8 patients months). Mean protein loss was 9.7 +/- 2.7 g per day. In 6 patients on IPD oral glucose tolerance test resulted in a paradoxical rise of HGH, whereas this was not observed after 4 months of CAPD.

Clinical dosimetry during cerebral arteriography.

Radiation dosimetry measurements on angiographer, X-ray technician and patient were performed during 18 femerocerebral angiograms. Lithium fluoride (LiF) thermoluminescent dosimeters were placed on various body areas to measure X-ray exposure. The results of this study indicate that radiation exposure received by medical personnel are well within the maximum permissible dose range established by the National Council of Radiation Protection. However, radiation exposure levels to radiosensitive areas of the patient are significant. A method to reduce patient exposure during femerocerebral arteriograms is suggested.

[Continous ambulatory peritoneal dialysis (CAPD)]. / Kontinuierliche ambulante Pertonealdialyse (CAPD).

Eleven patients were treated with continuous ambulatory peritoneal dialysis (CAPD) for periods of 2-7 months (48 patient-months). Clinical and biochemical control of uremia was adequate in all patients. Control of hypertension and serum phosphate level was easier than with previous intermittent peritoneal dialysis (IPD). Mean protein loss during CAPD was 9.7 +/- 2.7 g/day. Seven episodes of peritonitis occurred in 3 patients (1 peritonitis/6.8 months). General use of CAPD cannot be recommended until the high incidence of peritonitis is reduced by urgently needed technical improvements. A potential complication of CAPD was that triglycerides were markedly elevated in 4 patients.

Hemodynamic studies in long-term peritoneal dialysis patients.

A study was undertaken to evaluate the acute hemodynamic effects in ten patients from this clinic's long-term peritoneal dialysis program. With a Swan-Ganz catheter, the following parameters were measured in each patient during peritoneal dialysis: cardiac index, pulmonary artery pressure, right atrial pressure, inferior vena cava pressure, heart rate and arterial pressure. Mean predialysis cardiac index, stroke volume index and heart rate were normal. Predialysis pulmonary artery pressure and arterial pressure were slightly elevated. Mean weight loss during peritoneal dialysis was 1.6 kg. The most striking post-dialysis changes were a significant 20% decrease of the cardiac index and a 17% decrease of the pulmonary artery pressure. Heart rate and arterial pressure remained constant due to a 25% increase of total peripheral resistance. After filling the abdomen with one, two and three liters of dialysate, intra-abdominal pressure and inferior vena cava pressure increased up to 150 and 100%, respectively, whereas central hemodynamic parameters (pulmonary artery pressure, cardiac index, stroke volume index, heart rate and arterial pressure) were unchanged.

Central and peripheral haemodynamics in longterm peritoneal dialysis patients.

A study was undertaken in 11 longterm peritoneal dialysis (PD) patients to evaluate the acute haemodynamic effects of PD. After filling the abdomen with 1, 2 and 3L of dialysate, intra-abdominal pressure and inferior vena cava pressure increased up to 140 and 98% respectively, whereas central haemodynamic parameters were unchanged. Venous capacity decreased by 18%. Mean weight loss during PD was 1.6kg. The most striking post-PD changes were a significant 19% decrease of cardiac index and 18% decrease of pulmonary artery pressure. Heart rate and arterial pressure remained constant due to a 24% increase in total peripheral resistance.