Ceftobiprole is a broad-spectrum cephalosporin. The objective of this study was to test the hypothesis that the pharmacokinetics (PK) and exposure of ceftobiprole in Asian subjects are similar to those in non-Asian subjects. Three approaches were followed. The first compared the individual PK estimates between the 2 subgroups derived from a population PK model previously built. Next, it was determined whether “Asian subject” was a significant covariate. Finally, a pharmacodynamic analysis was performed by comparing measures of exposure and target attainment. No significant differences were found between PK parameter estimates for Asian and non-Asian subjects, with median values (range) for clearance of 4.82 L/h (2.12–10.47) and 4.97 L/h (0.493–20.6), respectively (P =.736). “Asian subject” was not a significant covariate in the population PK model. There were no significant differences between the measures of exposure. The geometric mean ratio for the fAUC was 1.022 (90%CI, 0.91–1.15), indicating bioequivalence. Taking a target of 60% coverage of the dose interval, more than 90% of the population in both subgroups was adequately exposed. This analysis demonstrated that there are no PK or pharmacodynamic differences between Asian and non-Asian subjects for a ceftobiprole dose of 500 mg every 8 hours as a 2-hour infusion.

Additional Metadata
Keywords cephalosporin, drug development, exposure, population pharmacokinetics, special patient population
Persistent URL dx.doi.org/10.1002/cpdd.465, hdl.handle.net/1765/110263
Journal Clinical Pharmacology in Drug Development
Muller, A.F, Punt, N, Engelhardt, M. (M.), Schmitt-Hoffmann, A.H. (A. H.), & Mouton, J.W. (2018). Pharmacokinetics and Target Attainment of Ceftobiprole in Asian and Non-Asian Subjects. Clinical Pharmacology in Drug Development, 7(7), 781–787. doi:10.1002/cpdd.465