Pharmacokinetics and Target Attainment of Ceftobiprole in Asian and Non‐Asian Subjects

Abstract

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.

Ceftobiprole: drug evaluation and place in therapy

“…A recent population pharmacokinetic/pharmacodynamic analysis demonstrated that at the standard ceftobiprole dose of 500 mg every 8 h as a 2-h infusion no pharmacokinetic or pharmacodynamic differences existed between Asian and non-Asian subjects, considering that, at a pharmacodynamic target of 60% t> MIC of the dosing interval, more than 90% of the population was adequately exposed in both subgroups [36].…”

A Phase 3, Randomized, Investigator-blinded Trial Comparing Ceftobiprole With a Standard-of-care Cephalosporin, With or Without Vancomycin, for the Treatment of Pneumonia in Pediatric Patients

“…Racial homogeny of the study population may also limit applicability of the results, although this is mitigated by the fact that the pathophysiology of pneumonia does not differ between racial groups and the pharmacokinetic profile of ceftobiprole is not altered by ethnicity. 21 , 36 …”

A Post Hoc Analysis of Two Phase III Trials Showing the Efficacy and Tolerability of Ceftobiprole in East Asian Patients

“…Overall, no significant differences in the pharmacokinetics or pharmacodynamics of ceftobiprole 500 mg administered every 8 h as a 2-h intravenous (iv.) infusion were observed [22]. Median clearance was 4.82 l/h (range, 2.12-10.47) in Asian patients and 4.97 l/h (range, 0.493-20.6) in non-Asian patients (p = 0.736), and no significant difference was reported in terms of exposure, with bioequivalence indicated via a geometric mean ratio for the area under the unbound drug concentrationtime curve of 1.022 (90% CI: 0.91-1.15) [22].…”

“…infusion were observed [22]. Median clearance was 4.82 l/h (range, 2.12-10.47) in Asian patients and 4.97 l/h (range, 0.493-20.6) in non-Asian patients (p = 0.736), and no significant difference was reported in terms of exposure, with bioequivalence indicated via a geometric mean ratio for the area under the unbound drug concentrationtime curve of 1.022 (90% CI: 0.91-1.15) [22]. A probability of target attainment was >90% in both Asian and non-Asian patients for broad-spectrum coverage with unbound drug concentration exceeding a conservative minimum inhibitory concentration of 4 mg/l for 60% of the dosing interval [22].…”

“…The pharmacokinetic profile of ceftobiprole has been compared between Asian (n = 47) and non-Asian (n = 153) patients [22] using data from a Phase III study in complicated skin and soft tissue infections [23], and a previously published pharmacokinetic analysis of the HAP study [24]. Overall, no significant differences in the pharmacokinetics or pharmacodynamics of ceftobiprole 500 mg administered every 8 h as a 2-h intravenous (iv.)…”