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.Cefoperazone, cefotaxime, and moxalactam are three newly developed cephalosporins with a high level of resistance to P-lactamase hydrolysis and a broad range of antibacterial action (13,18,28). The purpose of the present study was to compare the pharmacokinetics of these cephalosporins after a single intravenous (i.v.) bolus injection.
MATERIALS AND METHODSSubjects. Ten healthy volunteers, five males and five females, 21 to 51 years of age (mean, 32 years of age), 44 to 82 kg (mean, 66.7 kg), participated as test subjects. Informed written consent was obtained from each subject.Administration of antibiotics. Cefoperazone sodium (Ch.-BI 130) was supplied by Pfizer GmbH, Karlsruhe, Federal Republic of Germany; moxalactam disodium (Ch.-BI-4473-9C) by E. Lilly Giessen, and cefotaxime (batch no. 100 N31) by Hoechst AG, Frankfurt, Federal Republic of Germany. The compounds were reconstituted in sterile water just before administration. Each subject received 1.0 g of cefoperazone, cefotaxime, and moxalactam by an i.v. injection over 3 min. The antibiotics were given by random allotment with a 1-to 2-week interval between the injections.Sampling. Blood samples were taken over 12 h: before injection; after 5, 10, 20, 30, and 45 min; and after 1, 1.5, 2, 3, 4, 6, 8, and 12 h. Blood specimens were centrifuged at 4°C after clotting at room temperature. Urine was collected 0 to 3, 3 to 6, 6 to 12, and 12 to 24 h after dosage.An...
