Pharmacokinetics of ceftazidime in sheep and its penetration into tissue and peritoneal fluids

Abstract

Serum, tissue and peritoneal fluid concentrations of ceftazidime were studied in ewes after intravenous, intramuscular and subcutaneous administration at 50 mg kg −1 bodyweight. Tissue and peritoneal cages were implanted in the animals studied. After intravenous bolus administration, the mean serum concentration versus time profile was best described by a two-compartment open model. The distribution rate constant (α) was 3·5 ± 1·1 h −1 and the half-life ( t 1 2 α ) 0·22 ± 0·09 hour. The elimination rate constant (β) was 0·43 ± 0·04 h −1 and half-life t 1 2 β ) 1·6 ± 0·2 hours. The area under the curve was 275·7 ± 84·0 μg.ml −1 h. The volume of distribution as steady state was 356·1 ± 208·0 ml kg −1. The penetration ratio into tissue fluid was 62·6 ± 15·1 per cent and into peritoneal fluid 61·1 ± 16·5 per cent. After intramuscular injection, the elimination half-life was 1·7 ± 0·2 hours, the area under the curve was 228·7 ± 43·3 μg.ml −1 h. and the elimination rate constant was 0·42 ± 0·05 h −1. The penetration ratio into tissue fluid was 68·5 ± 37·3 per cent and into peritoneal fluid 73·3 ± 34·4 per cent. After subcutaneous injection, the elimination half-life was 1·8 ± 0·5 hours, the area under the curve was 231·8 ± 65·6 μg.ml −1 h. and the elimination constant was 0·41 ± 0·10 h −1 The penetration ratio into tissue fluid was 47·2 ± 3·5 per cent and into peritoneal fluid 58·1 ± 15·6 per cent. The degree of penetration into tissue and peritoneal fluids following a single intravenous, intramuscular or subcutaneous injection of ceftazidime in sheep was high.