PHARMACOKINETICS OF CEFAZOLINE AND DIBENZYLAMINE ADMINISTERED IN A SUSTAINED DRUG DELIVERY SYSTEM TO HEALTHY-VOLUNTEERS

The fate of cefazoline and dibenzylamine following intramuscular injection of a sustained release formulation containing sodium cefazoline: cefazoline-dibenzylamine (1:4) at a total dose of 1250 mg was characterized in eight healthy volunteers. Cefazoline and dibenzylamine levels in plasma were determined by HPLC and GLC techniques respectively. Kinetic analysis of the experimental results was performed using a sustained release model for both substances. The maximum plasma levels reached after administration proved to be 50.33 +/- 24.33-mu-g/ml at 1.33 +/- 0.52 h for cefazoline and 197.26 +/- 136.47 ng/ml at 5.60 +/- 3.23 h for dibenzylamine. These findings are a result of the inclusion in the formulation of a fraction of antibiotic subject to immediate release that permits a rapid increase in the plasma levels of cefazoline. The release rate constant of both substances from the derivative has a mean value of 0.095 +/- 0.047 h-1. This value is not statistically different (p > 0.005) from those of the rate constants governing the disappearance of the antibiotic and dibenzylamine from plasma calculated by the non-compartmental approach. Such findings show that the release of cefazoline and dibenzylamine from the sustained release portion is the rate limiting step in the absorption process and the apparent rate constants calculated from the slope of the terminal phases of the plasma levels curves reflect the value of the release constant of the substances from the derivative. The elimination half-life value of cefazoline calculated from the slope of the terminal phase of the plasma levels curve is significantly higher than that of the conventional formulation. This modification in the elimination half-life allows one to modify the dosage intervals to 24 h, ensuring therapeutic efficiency of treatment.