Penetration of eight beta-lactam antibiotics into the peritoneal fluid. A pharmacokinetic investigation

D. H. Wittman and H. H. Schassan

Serial serum and peritoneal fluid samples were taken after intravenous injection of cefuroxime sodium, cefoxitin sodium, cefotaxime sodium, cefoperazone sodium, ceftazidime, moxalactam disodium, mezlocillin sodium, and piperacillin sodium. Time-concentration curves were obtained for both pharmacokinetic compartments. The geometric mean of peritoneal fluid concentrations from eight to ten patients was used to define the time-concentrations curve for each substance. Serum pharmacokinetic values were calculated using an open two-compartment model. The concentrations (Cps) were calculated from peritoneal fluid concentrations by quadratic interpolation. The time for which one fourth of the Cp (Cp1/4) is maintained within the peritoneal cavity varied according to the substance and can be used to estimate dosage intervals. The Cp1/4 was compared with the minimal inhibitory concentrations for 1,344 pathogens encountered in 415 intra-abdominal infections from 31 studies.