Single-dose pharmacokinetics of meropenem in porcine cancellous bone determined by microdialysis

Abstract

Objectives Meropenem may be an important drug in the treatment of open tibial fractures and chronic osteomyelitis. Therefore, the objective of this study was to describe meropenem pharmacokinetics in plasma, subcutaneous adipose tissue (scT), and cancellous bone using microdialysis in a porcine model. Methods six female pigs were assigned to receive 1000 mg of meropenem intravenously over five minutes. Measurements of meropenem were obtained from plasma, scT, and cancellous bone for eight hours thereafter. Microdialysis was applied for sampling in solid tissues. The meropenem concentrations were determined using ultra-high-performance liquid chromatography. Results The penetration of meropenem into cancellous bone, expressed as the ratio of plasma to cancellous bone area under the concentration-curve from zero to the last measured value, was incomplete and delayed. The time with concentration above the minimal inhibitory concentration (T>MIc), for an MIc of 0.5 μg/ml, was shorter for cancellous bone in comparison with both plasma and scT. For MIcs above 0.5 μg/ml, T>MIc in cancellous bone was only shorter than scT. considering an MIc of 4 μg/ml, no animals achieved the target of 40% T>MIc in plasma and cancellous bone, while less than 20% achieved it in scT. Conclusion The main finding of this study was short T>MIc in cancellous bone after intravenous administration of 1000 mg meropenem. consequently, in order to achieve sufficient tissue concentration in the cases of open tibial fractures and chronic osteomyelitis, supplemental application of meropenem may be necessary.