title: An open-label, non-randomised, phase 1, single-dose study to assess the pharmacokinetics of ceftaroline in patients with end-stage renal disease requiring intermittent haemodialysis.
abstract: For patients with normal renal function, the recommended ceftaroline fosamil dose is a 600 mg 1-h intravenous (i.v.) infusion every 12 h (q12h). In patients with a creatinine clearance of ≤30 mL/min, including those with end-stage renal disease (ESRD), the recommended dose is a 200 mg 1-h i.v. infusion q12h. This phase 1 study (NCT01664065) evaluated the pharmacokinetics, safety and tolerability of ceftaroline fosamil 200 mg 1-h i.v. infusion in patients with ESRD. Patients with ESRD (n=8) participated in two treatment periods (ceftaroline fosamil 200 mg administered pre- and post-haemodialysis) separated by >1 week. Healthy volunteers (n=7) received a single 600 mg dose of ceftaroline fosamil. Blood (pre- and post-haemodialysis) and dialysate samples were obtained for pharmacokinetic analysis. In patients with ESRD, the geometric mean [coefficient of variation (%CV)] plasma ceftaroline area under the plasma concentration-time curve from zero to infinity (AUC0-∞) following post-haemodialysis ceftaroline fosamil 200 mg infusion was 64.8 (38.9)μg·h/mL, similar to that in volunteers following a 600 mg infusion [62.7 (9.4)μg·h/mL]. Ceftaroline AUC0-∞ decreased by ca. 50% when infusion was initiated pre-haemodialysis. In the pre-haemodialysis treatment period, 80% of the ceftaroline fosamil dose was recovered in dialysate as ceftaroline (73%) and ceftaroline M-1 (7%). The frequency of adverse events was similar across patients with ESRD (pre- and post-haemodialysis) and volunteers (43%, 50% and 43% of subjects, respectively). Ceftaroline fosamil 200 mg 1-h i.v. infusion q12h, administered post-haemodialysis on dialysis days, is an appropriate dosage regimen for ESRD patients.
authors.affiliation: Contractor at AstraZeneca, Wilmington, DE, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Sunzel
authors.affiliation: AstraZeneca, Macclesfield, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Learoyd
authors.affiliation: AstraZeneca, Waltham, MA, USA.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Li
authors.affiliation: AstraZeneca, Waltham, MA, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Quintiles, Overland Park, KS, USA.
authors.forename: Ngoc
authors.initials: N
authors.lastname: Ngo
authors.affiliation: AstraZeneca, Wilmington, DE, USA. Electronic address: timi.edeki@astrazeneca.com.
authors.forename: Timi
authors.initials: T
authors.lastname: Edeki
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002511:Cephalosporins / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D007676:Kidney Failure, Chronic; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D055815:Young Adult; D000097583:Ceftaroline
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000097583:Ceftaroline
keywords: Ceftaroline; Ceftaroline fosamil; End-stage renal disease; Pharmacokinetics; Renal impairment