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The pharmacokinetics of cefoperazone, cefotaxime, and moxalactam were compared in a cross-over randomized study in 10 healthy volunteers. Each subject received 1.0 g of the three drugs by bolus intravenous injection over 3 min. Serum and urine concentrations were assayed by a microbiological method and in addition by high-pressure liquid chromatography (HPLC) for cefotaxime in five subjects. Maximal concentrations in serum 5 min after the injection were 163 +/- 40.3 mg/liter for cefoperazone, 86.1 +/- 19.0 mg/liter for cefotaxime, and 95.5 +/- 21.1 mg/liter for moxalactam. After 12 h, 1.2 +/- 1.4 mg of cefoperazone per liter and 1.8 +/- 0.9 mg of moxalactam per liter could still be measured. Eight hours after the administration of cefotaxime, serum concentrations were below the detection limit of 0.3 mg/liter in most subjects. By HPLC analysis, the mean maximal concentration of desacetyl cefotaxime was 16.6 +/- 10.5 mg/liter 5 min after application; the metabolite exceeded the serum concentration of the parent compound after 1 to 2 h. Relevant pharmacokinetic parameters were calculated, using two- and three-compartment models. The terminal half-life was 144.1 +/- 37.3 min for cefoperazone, 76.1 +/- 32.0 min for cefotaxime, and 272.4 +/- 114.1 min for moxalactam. The apparent volume of distribution corresponded to the extracellular volume. Only 25.1 +/- 8% of cefoperazone could be detected in urine compared with 53.3 +/- 8.1% of cefotaxime and 61.0 +/- 9.2% of moxalactam in 24 h. A total of 89.6 +/- 11.4% of the cefotaxime dose could be recovered by HPLC in urine, 60.6 +/- 7.7% as cefotaxime and 29.1 +/- 7.0% as desacetyl cefotaxime.

Comparative pharmacokinetics of cefoperazone, cefotaxime, and moxalactam