DOS Kongressen 2014 ·
187
Pharmacokinetics of Cefuroxime in Bone,
Subcutaneous Tissue and Plasma – Comparison
of Continuous versus Short-term Infusion
Mikkel Tøttrup, Mats Bue , Kurt Fuursted, Tore Forsingdal Hardlei, Kjeld Søballe,
Hanne Birke-Sørensen
Department of Orthopaedic Surgery and Orthopaedic Research Unit in
Aarhus, Hospitalunit Horsens and Aarhus University Hospital; Department
of Orthopaedic Surgery Orthopaedic Research Unit in Aarhus, Hospitalunit
Horsens and Aarhus University Hospital; , Statens Serum Institute; Department
of Clinical Biochemistry, Aarhus University Hospital; Department of
Orthopaedic Surgery, Aarhus University Hospital; Orthopaedic Research Unit,
Aarhus University Hospital
Background:
The relatively short half-lives of most beta-lactams suggest that
continuous infusion (CI) of these time-dependent antibiotics may be favourable
compared to short-term infusion (STI). Nevertheless, only limited pharmacoki-
netic (PK) data is available to support this theory, particularly in solid tissues like
bone.
Purpose / Aim of Study:
To obtain PK parameters of cefuroxime in plasma,
subcutaneous tissue (SCT) and bone in pigs receiving 1500 mg of cefuroxime
administered either as STI or as CI, and to compare time above minimal inhibi-
tory concentrations (T > MIC) between the two groups.
Materials and Methods:
Twelve pigs were included. Each animal was randomly
assigned to receive 1500 mg of cefuroxime either as STI or CI. Measurements
of cefuroxime were conducted in plasma, SCT, cancellous and cortical bone ev-
ery 30 min. The measurements in solid tissues were conducted using microdi-
alysis. A two-compartment population model was fitted to the drug concentra-
tion data separately for the different tissues using a non-linear mixed effects
regression model. Key pharmacokinetic parameters and T > MIC were estimated
using Monte Carlo simulations.
Findings / Results:
Except for SCT in the STI group, tissue penetration was
impaired for all tissues. The poorest tissue penetration was found in bone. Both
tissue area under the curves and tissue penetration ratios generally appeared to
be lower in the CI group. Nevertheless, significantly longer T > MIC was found
for CI up until MICs of 4, 2, 2 and 0.5 μg/mL for plasma, SCT, cancellous and
cortical bone respectively.
Conclusions:
CI of beta-lactams with short half-lives may be favourable com-
pared to STI if dosed appropriately. The poorest tissue penetration was found in
bone. The high rate of treatment failure for osteomyelitis may therefore partly
be attributable to impaired target site penetration of antibiotics.
134.
