Pharmacokinetic model for cefazolin distribution during total hip arthroplasty in dogs

Objectives - To compare cefazohn pharmacokinetics in serum and concentrations in tissues during total hip arthroplasty in dogs with and without 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 and tissue specimens from the coxofemoral joint capsule, acetabulum, and femur were obtained during unilateral total hip arthroplasty. Cefazolin concentrations in serum and tissue specimen supernatant were determined, using high-performance liquid chromatography, for use in pharmacokinetic analysis. Mathematical simulation of serum cefazolin concentrations was used to to predict the optimal dose. Results - Mean pharmacokinetic constants (SEM) were 0.146 (0.013) min^-1 for α. 4.74 min for t_1/2α, 0.015 (0.004) min^-1 for β, and 46.83 mm for t_1/2β. Significant difference was not detected for cefazolin distribution and elimination between dogs with and without hip dysplasia. Additionally, significant difference was not observed in pharmacokinetic parameters describing distribution and elimination between the first and second doses of cefazolin The predicted optimal dosage regimen was 8 mg/ kg of body weight, IV, every hour or 22 mg/kg, IV, every 2 hours. 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 at least 10X the minimum inhibitory concentration for 3 to 4 hours.