A. Jacolot P. Incagnoli A.R. Edouard M. Tod O. Petitjean K. Samii O. Mimoz Pharmacokinetics of cefpirome during the posttraumatic systemic inflammatory response syndrome Received: 3 September 1998 Final revision received: 18 January 1999 Accepted: 25 February 1999 Presented in part at the 39th Congrs National d'AnesthØsie-RØanimation, Paris, 25±28 September, 1997 (abstr no. 328). This work was supported in part by a grant from Nicole Szumeraj, Laboratoires Roussel Diamant, Paris-La DØfense, France A. Jacolot ´ P. Incagnoli ´ A.R. Edouard ´ K. Samii ´ O. Mimoz ( ) ) Service d'AnesthØsie-RØanimation, Hôpital Bice à tre, F-94 270 Le Kremlin Bice à tre, France A. Jacolot ´ M. Tod ´ O. Petitjean Centre de Recherche en Pathologie Infectieuse et Tropicale (CrØpit 93), F-93009 Bobigny, France Mailing address: Service d'AnesthØsiologie, Hôpital Paul Brousse, F-94 804 Villejuif CØdex, France e-mail: olivier.mimoz@pbr.ap-hop-paris.fr Tel. + 33 (1) 45 59 32 19 Fax + 33 (1) 45 59 38 34 Abstract Objective: To determine the pharmacokinetic parameters of cefpirome, a new so-called fourth- generation cephalosporin, in previ- ously healthy trauma patients with posttraumatic systemic inflammato- ry response syndrome (SIRS) and to compare them to parameters ob- tained in matched, healthy volun- teers. Design: A prospective study. Setting: 12-bed surgical intensive care unit in a university hospital. Patients: 9 severe [Injury Severity Score, median (range) 29 (16±50)] trauma patients on mechanical ven- tilation with proven or suspected cefpirome-susceptible nosocomial infection, with no renal or hepatic failure, and healthy volunteers matched for age (  5 years), sex, and body surface area (  10 %) were enrolled. All were men. Interventions: Cefpirome (2 g twice daily) was continuously infused over a 0.5 h period alone or concomitant- ly with ciprofloxacin (400 mg over 1 h, twice daily). Measurements and main results: An- tibiotic concentrations in plasma were measured by high-perfor- mance liquid chromatography; their pharmacokinetic parameters were evaluated at 12 time points after the first drug administration using a noncompartmental model. Cef- pirome pharmacokinetic parame- ters for the two groups were similar despite a wider variation for trauma patients. Specifically, the median (range) time during which the cef- pirome concentration in plasma re- mained over 4 mg/l (corresponding to the French lower cutoff deter- mining cefpirome susceptibility) was 9.5 (7± > 12) and 9 (8±12) h for trau- ma patients and healthy volunteers, respectively. In the group of five pa- tients receiving combined antibiotic therapy, the interindividual variabil- ity of pharmacokinetics was wider for ciprofloxacin than for cefpirome. Conclusion: No major pharmacoki- netic modification was noted when cefpirome was given to trauma pa- tients with posttraumatic SIRS without significant organ failure, in- dicating that no dosage adjustment seems required in this population. However, larger studies including determination of antibiotic levels in tissues are warranted to confirm these results. Key words Cefpirome ´ Ciprofloxacin ´ Pharmacokinetics ´ Systemic inflammatory response syndrome ´ Trauma Intensive Care Med (1999) 25: 486±491 Ó Springer-Verlag 1999 ORIGINAL