Population pharmacokinetics of ceftaroline in patients with acute bacterial skin and skin structure infections or community-acquired bacterial pneumonia.

Abstract:

:Ceftaroline, the active form of ceftaroline fosamil, is a broad-spectrum cephalosporin antibiotic. A population pharmacokinetic (PPK) model for ceftaroline was developed in NONMEM® using data from 185 healthy subjects and 92 patients with acute bacterial skin and skin structure infection (ABSSSI). Data from 128 patients with community-acquired bacterial pneumonia (CABP) were used for external model validation. Healthy subjects received 50-2,000 mg ceftaroline fosamil via intravenous (IV) infusion over 1 hour or intramuscular (IM) injection q12h or q24h. ABSSSI and CABP patients received 600 mg of ceftaroline fosamil IV over 1 hour q12h. A three-compartment model with zero-order IV or parallel first-order IM input and first-order elimination described ceftaroline fosamil PK. A two-compartment model with first-order conversion of prodrug to ceftaroline and parallel linear and saturable elimination described ceftaroline PK. Creatinine clearance was the primary determinant of ceftaroline exposure. Good agreement between the observed data and both population (r(2)  = 0.93) and individual post-hoc (r(2)  = 0.98) predictions suggests the PPK model can adequately approximate ceftaroline PK using covariate information. Such a PPK model can evaluate dose adjustments for patients with renal impairment and generate ceftaroline exposures for use in pharmacokinetic-pharmacodynamic assessments of efficacy in patients with ABSSSI or CABP.

journal_name

J Clin Pharmacol

authors

Van Wart SA,Forrest A,Khariton T,Rubino CM,Bhavnani SM,Reynolds DK,Riccobene T,Ambrose PG

doi

10.1002/jcph.153

subject

Has Abstract

pub_date

2013-11-01 00:00:00

pages

1155-67

issue

11

eissn

0091-2700

issn

1552-4604

journal_volume

53

pub_type

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