A WEIBULL DISTRIBUTION MODEL FOR INTRADERMAL ADMINISTRATION OF CEFTAZIDIME

The pharmacokinetics of 1 g of ceftazidime administered intradermally was studied in seven healthy volunteers. The objective of the present study was to find the most appropriate mathematical model to describe the drug intake process. The concentration of ceftazidime in plasma was measured by HPLC. The disposition of the drug was described by a one-compartment pharmacokinetic model, with drug intake occurring by different processes: a zero-order process due to the administration and a first-order intake from the injection site to the systemic circulation. The Weibull model was considered as an approximation of the overall process. The mean Weibull parameters were td (time necessary to transfer 63% of the administered drug into the systemic circulation) of 2.75 +/- 0.75 h, and f (shape) of 1.04 +/- 0.15. The mean elimination half-life was 2.0 +/- 0.4 h. The area under the concentration versus time curve obtained in this study (139 +/- 46 mg . h/L) is very near to literature values reported after single intravenous doses of 1 g of ceftazidime, suggesting that the bioavailability of ceftazidime after intradermal administration may be approximately 100%. Moreover, the mean peak plasma concentration (37 +/- 16 mg/L) is in the same range as that reported in the literature after intramuscular administration of a single dose of 1 g.