[Pharmacokinetics of ceftazidime in healthy and renal failure subjects]. / Pharmacocinétique de la ceftazidime chez le sujet sain et chez l'insuffisant rénal.

Ceftazidime is poorly bound to plasma proteins, is not metabolized and is excreted mostly by glomerular filtration. Its elimination half-life is about 1.5-2 hours, and their kinetics are modified by renal impairment. The dosage recommended in adult is 1 to 2 g 8-hourly, to be adjusted to the needs of individual cases. The interval between doses must be extended to 12 hours in patients with mild renal impairment and to 36-48 hours in those with severe renal failure. A supplementary dose of ceftazidime is required at the end of each haemodialysis session. In patients under chronic peritoneal dialysis, the loading dose (10 mg/kg) is followed by continuous administration of 5 mg/kg into each dialysis cavity.

Pharmacokinetics of ceftazidime in normal and uremic subjects.

The pharmacokinetics of ceftazidime, administered as a single intravenous dose of 15 mg/kg given in a bolus injection over 3 min, were investigated in 5 normal subjects and in 19 uremic patients. The subjects studied were divided into five groups according to values for endogenous creatinine clearance (CLCR): group I, five subjects with CLCR greater than 80 ml/min; group II, five patients with CLCR = 30 to 80 ml/min; group III, six patients with CLCR = 10 to 30 ml/min; group IV, four patients with CLCR = 2 to 10 ml/min; and group V, four anuric patients on hemodialysis. A two-compartment open model was used to calculate the pharmacokinetic parameters. In normal subjects, the mean apparent elimination half-life was 1.57 +/- 0.13 h. The central distribution volume and the apparent volume of distribution were 0.127 +/- 0.023 and 0.230 +/- 0.015 liter/kg, respectively. Of the injected dose, 83.6 +/- 3.6% was eliminated in the urine as parent drug within 24 h. The terminal half-life increased with impairment of renal function to about 25 h in severely uremic patients. Impairment of function did not significantly modify the half-life at alpha phase, central distribution volume, or apparent distribution volume. A 6- to 8-h hemodialysis procedure reduced concentrations of ceftazidime in plasma by approximately 88%, and the elimination half-life was 2.8 +/- 0.2 h. There was no evidence of accumulation of ceftazidime in four patients with severe and chronic impairment of function who received doses of 0.5 to 1.0 g every 24 h for 10 days.

Ranitidine upon meal-induced gastric secretion: oral pharmacokinetics and plasma concentration effect relationships.

1 Ranitidine oral kinetics and plasma concentration-effect relationships upon meal-induced gastric secretion were investigated in normal subjects. Four oral doses of ranitidine (50, 100, 150 or 200 mg) and placebo were tested. 2 Oral ranitidine showed a terminal half-life of about 2 h 25 min. Maximal plasma level was about 240 ng/ml for a 100 mg dose, and occurred about 1 h after dose. From the range of 50 to 200 mg dose, no indication of non-linearity was observed in the drug kinetics. 3 Ranitidine administration resulted in a dose-related reduction in meal-stimulated acid secretion reaching, 46, 70, 82 and 92%, respectively. Mean ranitidine plasma concentrations producing 50 and 80% inhibition of acid secretion were 73 and 180 ng/ml, respectively, with great inter-individual variability. 150 and 200 mg ranitidine oral doses maintained IC50 for at least 4.5 and 5.5 h, respectively. Upon oral administration, ranitidine exerted no effect on gastric emptying of the meal but slightly decreased the gastrin response to the meal.