Vancomycin pharmacokinetics in patients with various degrees of renal function

The influence of age, protein binding, and renal function on the pharmacokinetics of intravenous vancomycin was evaluated in 37 adult patients with various degrees of renal function. Patients were categorized into three groups based on measured creatinine clearance (CL(CR)): groups 1, 2, and 3 had 24-h CL(CR)s of >70, 40 to 70, and 10 to 39 ml/min per 1.73 m², respectively. After 1 h of intravenous infusion, concentrations of vancomycin in serum declined in a biexponential manner in all patients. Diminished renal function in groups 2 and 3 was accompanied by a lower total body vancomycin clearance (CL) (52.6 and 31.3, respectively, versus 98.4 ml/min per 1.73 m²) and a lower renal vancomycin clearance (CL(R)) (48.2 and 19.8, respectively, versus 88.0 ml/min per 1.73 m²) than in group 1. No significant differences in apparent distribution volume of the central compartment or apparent distribution volume at steady state were observed. Mean serum protein binding of vancomycin was 30% and was not significantly affected by renal function. Stepwise multiple linear regression analysis revealed that CL(CR) was the strongest predictor of vancomycin CL (r = 0.77, P < 0.001) and vancomycin CL(R) (r = 0.87, P < 0.001). Age did not significantly improve these correlations once CL(CR) was included. The relationship of vancomycin CL and CL(CR) was utilized to develop the following equation to dose vancomycin in the majority of renally impaired patients: dose (milligrams per kilogram per 24 h) = 0.227 CL(CR) + 5.67, where CL(CR) is standardized to milliliters per minute per 70 kg. The practical dosing intervals that the calculated dose can be divided into and administered include 8, 12, 24, and 48 h based on the CL(CR) of the patient.