PHARMACOKINETIC MODEL FOR CEFAZOLIN DISTRIBUTION DURING TOTAL HIP-ARTHROPLASTY IN DOGS

Objectives-To compare cefazolin pharmacokinetics in serum and concentr ations in tissues during total hip arthroplasty in dogs with and witho ut hip dysplasia, and to calculate the optimal dosage of cefazolin for prophylactic use during total hip arthroplasty. Animals-10 dogs with hip dysplasia and 3 clinically normal dogs. Procedure-Blood samples an d tissue specimens from the coxofemoral joint capsule, acetabulum, and femur were obtained during unilateral total hip arthroplasty. Cefazol in concentrations in serum and tissue specimen supernatant were determ ined, using high-performance liquid chromatography, for use in pharmac okinetic analysis. Mathematical simulation of serum cefazolin concentr ations was used to to predict the optimal dose. Results-Mean pharmacok inetic constants (SEM) were 0.146 (0.013) min(-1) for alpha, 4.74 min for t(1/2 alpha), 0.015 (0.004) min(-1) for beta, and 46.83 min for t( 1/2 beta). Significant difference was not detected for cefazolin distr ibution and elimination between dogs with and without hip dysplasia. A dditionally, significant difference was not observed in pharmacokineti c parameters describing distribution and elimination between the first and second doses of cefazolin. The predicted optimal dosage regimen w as 8 mg/kg of body weight, IV, every hour or 22 mg/kg, IV, every 2 hou rs. Clinical Relevance-For prophylactic IV treatment during total hip arthroplasty, use of cefazolin at a dosage of 8 mg/kg every hour or 22 mg/kg every 2 hours should maintain serum cefazolin concentrations al least 10x the minimum inhibitory concentration for 3 to 4 hours.