Population pharmacokinetics of vancomycin in orthopaedic patients

Aim: The objective of this study was to evaluate the pharmacokinetic properties of vancomycin in orthopaedic patients during routine clinical care using a non-linear mixed effects modelling approach.

Methods: A two-compartment infusion model with first-order elimination was fitted to serum vancomycin concentration data (n = 1198 points) obtained retrospectively from routine therapeutic drug monitoring records of 132 orthopaedic patients. Vancomycin concentrations were determined by an in vitro chemiluminescent microparticle immunoassay (CMIA). Measurement of serum creatinine levels were performed using the Jeffe Kinetic method standardized by isotope dilution mass spectrometry. Several GFR estimation (eGFR) formulas were assessed during model development.

Results: A linear relationship between the clearance of vancomcyin and the eGFR was found. For a typical 70 kg man, vanocmycin clearance (CL) was: 0.0437 x CKD-EPI eGFR + 0.1348 L/h, where CKD-EPI eGFR was the estimated glomerular filtration rate using CKD-EPI formula, and 0.1348 was the non-renal clearance. The central volume of distribution (V1), and the peripheral volume of distribution (V2) were 54.9 L and 43.9 L, respectively. The intercompartment clearance (Q) was 1.18 L/h. The predictive performance of this population model for vancomcyin serum concentrations would appear suitable for clinical purposes.

Conclusion: This study highlighted that the CKD-EPI eGFR significantly influences vancomycin elimination.