Exploring the Use of C-Reactive Protein to Estimate the Pharmacodynamics of Vancomycin

Background: C-reactive protein (CRP) pharmacodynamic (PD) models have the potential to provide adjunctive methods for predicting the individual exposure response to antimicrobial therapy. We investigated CRP PD linked to a vancomycin pharmacokinetic (PK) model using routinely collected data from noncritical care adults in secondary care. Methods: Patients receiving intermittent intravenous vancomycin therapy in secondary care were identified. A 2-compartment vancomycin PK model was linked to a previously described PD model describing CRP response. PK and PD parameters were estimated using a Non-Parametric Adaptive Grid technique. Exposure–response relationships were explored with vancomycin area-under-the-concentration-time-curve (AUC) and EC50 (concentration of drug that causes a half maximal effect) using the index, AUC:EC50, fitted to CRP data using a sigmoidal Emax model. Results: Twenty-nine individuals were included. Median age was 62 (21–97) years. Fifteen (52%) patients were microbiology confirmed. PK and PD models were adequately fitted (r2 0.83 and 0.82, respectively). There was a wide variation observed in individual Bayesian posterior EC50 estimates (6.95–48.55 mg/L), with mean (SD) AUC:EC50 of 31.46 (29.22). AUC:EC50 was fitted to terminal CRP with AUC:EC50>19 associated with lower CRP value at 96–120 hours of therapy (100 mg/L versus 44 mg/L; P
Source: Therapeutic Drug Monitoring - Category: Drugs & Pharmacology Tags: Original Article Source Type: research