Safety, local tolerability and pharmacokinetics of ceftaroline fosamil administered in a reduced infusion volume.

ABSTRACT: The standard dose of ceftaroline fosamil for patients with normal renal function is 600?mg diluted in 250?ml by 60?min intravenous infusion every 12?h. This two part phase I trial (NCT01577589) assessed safety and local tolerability of multiple ceftaroline fosamil 50?ml and 250?ml infusions, and pharmacokinetics following single administrations of each infusion volume.Part A was a placebo-controlled, double-blind, multiple dose crossover study. Twenty-four healthy subjects were randomized to simultaneous, bilateral ceftaroline fosamil 600?mg and placebo infusions in each arm (50?ml then 250?ml or vice versa) every 12?h for 72?h, with a ? 4.5 day washout. Local tolerability was evaluated by the Visual Infusion Phlebitis scale, with scores ?2 considered infusion site reactions (ISRs). Part B was an open label crossover study. Ten subjects were randomized to single 50?ml and 250?ml ceftaroline fosamil 600?mg infusions on days 1 and 3 (washout on day 2). Blood samples for pharmacokinetic analysis were taken over 24?h.In part A, four subjects (16.7%) experienced ISRs, all of which were associated with placebo infusions. No ISRs were reported for either ceftaroline fosamil 50?ml or 250?ml. Plasma pharmacokinetics (ceftaroline fosamil, active ceftaroline and an inactive metabolite) were similar following single 50?ml and 250?ml infusions in part B.No new safety concerns were identified for ceftaroline fosamil 600?mg 50?ml compared with 250?ml. These findings suggest infusion volumes down to 50?ml may be used in patients with fluid intake restrictions.

SUBMITTER: Edeki T 

PROVIDER: S-EPMC4256619 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature