Pharmacokinetic comparison of 5 g of azlocillin every 8 h and 4 g every 6 h in healthy volunteers.

To compare the multiple-dose pharmacokinetics of two dosage regimens of azlocillin, we studied 12 healthy volunteers via a randomized, crossover design with a 2-week washout phase between regimens. Serum and urine samples were collected for 8 h following the fifth dose of a regimen of 4 g every 6 h and the fourth dose of a regimen of 5 g every 8 h. Data for concentrations in serum were fitted to a two-compartment open model by nonlinear regression. Statistically significant differences (P less than 0.05) were observed in the following parameters (mean +/- standard deviation) for the 4- and 5-g regimens, respectively: area under the serum concentration-time curve during the dosing interval, 592 +/- 140 versus 772 +/- 151 micrograms.h/ml; terminal elimination rate constant, 0.5364 +/- 0.0912 versus 0.4758 +/- 0.0486 h-1; renal clearance, 87.6 +/- 16.1 versus 76.1 +/- 13.5 ml/min; maximum drug concentration in serum, 381 +/- 89 versus 473 +/- 90 micrograms/ml; and minimum drug concentration in serum, 19 +/- 10 versus 8 +/- 4 micrograms/ml. No significant differences were seen in the following parameters: V1, V beta, k10, k12, k21, total systemic clearance, and nonrenal clearance. These data support the presence of saturable renal elimination of azlocillin, as well as the feasibility of an 8-h dosing interval.

[The effect of infusion rate on pharmacokinetic parameters of azlocillin and mezlocillin]. / Uber die Bedeutung der Applikationsgeschwindigkeit für die pharmakokinetischen Parameter von Azlocillin und Mezlocillin.

Azlocillin (Securopen) and mezlocillin (Baypen) were given to 3 healthy subjects as intravenous infusion. The dose of 4 g was administered to each person within 5, 15, and 30 min in a randomized crossover design. Using HPLC the unchanged penicillin antibiotics were determined quantitatively, their metabolites were assessed qualitatively. The same specimens were also studied by means of a bioassay (agar diffusion technique). Both methods yielded similar serum and urine concentrations besides the urinary excretion of azlocillin. Here the bioassay measured higher amounts indicating an antibacterially active metabolite being excreted in the urine. No dependence upon infusion time was found. Since both drugs were tested with the same dosis in the same subjects, their pharmacokinetic parameters could be compared: mezlocillin, being more lipophilic than azlocillin, showed a higher volume of distribution and therefore lower serum concentrations. Renal clearance was the same for both drugs, but mezlocillin was excreted to a smaller extent in the urine. Higher total clearance and shorter elimination half-life of mezlocillin indicate a greater extrarenal elimination. The results suggest fast application of both penicillins. There is no pharmacokinetic reason for a prolongation of infusion times.