Pharmacokinetics of ceftazidime after regional limb perfusion in standing horses

Abstract

Objective: To determine the metacarpophalangeal joint fluid concentrations of ceftazidime administered via regional limb perfusion (RLP).

Animals: Eight healthy horses.

Methods: RLP was performed by injecting 2 g of ceftazidime and 60 mL of perfusate volume in the cephalic vein of standing, sedated horses. Serum and synovial fluid from the metacarpophalangeal joint were collected before perfusion and at 0.5, 2, 6, 12, 24 hours postperfusion. Ceftazidime concentrations were measured via liquid chromatography. Maximal concentration (C_max ), area under the curve (AUC), half-life of the drug (T ½), and the timing of C_max (T_max ) were determined to assess ceftazidime as a candidate drug for RLP. Continuous parameters were compared with the Mann-Whitney U test. P value ≤ .05 was considered statistically significant.

Results: The C_max of ceftazidime in synovial fluid (235 µg/mL) was 15 times higher than the minimal inhibitory concentration (MIC) for most bacteria involved in orthopedic infections, including resistant pathogens such as Pseudomonas aeruginosa (MIC = 16 µg/mL). However, synovial concentrations decreased quickly and remained above the MIC in only 1 horse by 6 hours postperfusion.

Conclusion: RLP generated high synovial fluid concentrations of ceftazidime in the distal limb, but these concentrations decreased rapidly below the deliberately high MIC selected.

Clinical relevance: Once daily RLP, as applied in our study, with 2 g ceftazidime in standing horses, cannot be recommended for use in a clinical setting.