Influence of urinary sodium on calcium excretion in normal individuals. A redefinition of hypercalciuria.

The twenty-four hour urinary excretion of calcium and sodium was measured in 38 normal volunteers after a week on a diet containing 400 mg of calcium per day. There was a significant correlation (P less than 0.001) between calcium and sodium excretion. The normal range of calcium excretion as a function of sodium excretion has been determined. This approach sharpens the definition of hypercalciuria by taking into account the influence of dietary sodium intake. It also removes the necessity of regulating dietary sodium as well as calcium intake before measuring calcium excretion in patients who form recurrent renal stones.

Metronidazole pharmacokinetics in patients with acute renal failure.

The pharmacokinetics and metabolism of intravenous metronidazole were studied in six patients with acute renal failure. In two of the patients a single dose (500 mg) of metronidazole was administered, whereas in four patients the steady-state pharmacokinetics were studied after four days therapy of 500 mg twice daily. Plasma concentrations of metronidazole and its hydroxy and acetic acid metabolites were measured by a specific and sensitive HPLC method. The volume of distribution was 0.65 +/- 0.13 l/kg (mean +/- S.D.), elimination half-life was 9.9 +/- 2.5 h and total plasma clearance was 55.5 +/- 17.7 ml/min. Renal clearance was almost non-existent (1.4 +/- 1.4 ml/min), whereas non-renal clearance was 54.0 +/- 18.2 ml/min. Steady-state plasma concentrations of metronidazole were 15.3 +/- 3.8 mg/l, the hydroxy metabolite were 17.4 +/- 2.0 mg/l and the acetic acid metabolite were 1.2 +/- 0.8 mg/l. In the patients studied, a dosing regimen of 500 mg twice daily resulted in therapeutically adequate blood levels of metronidazole.

Elimination of amphotericin B in impaired renal function.

The influence of impaired renal function on the steady-state plasma clearance of amphotericin B was determined in seven patients with creatinine clearances ranging from zero to normal. Contrary to previous reports, steady-state plasma concentrations of total drug were lower in uremic patients than in patients with normal renal function. Total plasma clearance of amphotericin B ranged from 16.7 to 39.9 ml/min, correlated directly with the plasma creatinine concentration, and correlated inversely with the creatinine clearance. Urinary excretion of unchanged drug accounted for less than 10% of the dose. In 10 healthy subjects, mean percent of amphotericin B unbound in plasma was 3.55 +/- 0.32 (SD). Binding was determined in a further group of 10 uremic patients. Mean unbound percent (4.15 +/- 0.73, SD) was higher than in the healthy subjects, and the binding ratio (molar concentration of bound to unbound drug) correlated weakly with the creatinine clearance. This suggests that plasma clearance of unbound amphotericin B and, therefore, steady-state plasma concentrations of unbound drug are not affected by renal impairment, and that dosage requirements will be overestimated if based on measurements of total drug plasma concentration.

Disposition and removal of metronidazole in patients undergoing haemodialysis.

The pharmacokinetics and haemodialysis clearance of metronidazole were investigated in four renal failure patients after a single 500 mg intravenous dose and in two renal failure patients on continuous treatment with metronidazole. During dialysis, the volume of distribution of metronidazole was 0.60 +/- 0.04 l/kg, total clearance was 196.0 +/- 60.6 ml/min and the elimination half-life had an harmonic mean of 2.14 h. Extraction across the dialyser was 51.5 +/- 7.8% and was limited to the distribution of drug in plasma water. Dialysis clearance was 125.0 +/- 32.7 ml/min, which represented 62 +/- 6% of total clearance and was 1.75 times the sum of the other clearance mechanisms. The hydroxy metabolite was extracted and cleared by the dialyser to the same degree as metronidazole itself. During the 4 h-dialysis 44.9 +/- 2.6% of the dose was removed by the dialyser in the four patients administered a single dose. Metronidazole is efficiently cleared and extensively removed by dialysis, and therefore dosage adjustments and alterations in the timing of dosage administration are essential in patients undergoing haemodialysis.

Hemodialysis, peritoneal dialysis, plasmapheresis and forced diuresis for the treatment of quinine overdose.

Peritoneal dialysis, hemodialysis, plasma exchange and forced diuresis have been reported to accelerate removal of quinine following quinine poisoning. All these modalities were used simultaneously to treat a 19 year old youth who had become blind as a result of an overdose of quinine tablets. The serum quinine level was measured at 10.5 microgram/ml 13 hours after quinine ingestion. Forced diuresis accounted for the removal of 557 mg of quinine in the first 5 hours and a total of 1625 mg over 75 hours., A 6 hour hemodialysis recovered 30 mg of quinine while peritoneal dialysis removed an average of 1.6 mg/hr over the first 48 hours. Plasmapheresis over 3 hours exchanged 2 liters of plasma containing a total of 8.5 mg of quinine. Some vision returned 19 hours after quinine ingestion but did not become normal until 5 1/2 months later. We conclude that, hemodialysis, peritoneal dialysis and plasma exchange made only a minor contribution to quinine elimination by comparison with renal excretion of quinine.