Population pharmacokinetics of teicoplanin in patients and simulation of trough concentrations after various initial loading doses

We performed a population pharmacokinetics study of teicoplanin and a simulation of trough concentrations after various initial loading doses. Data for the study were collected from 220 patients treated intravenously with teicoplanin for infection of detected or suspected MRSA or other methicillin-resistant Gram positive cocci. We evaluated population means for the pharmacokinetic parameters of total body clearance, CL (L/h), and volume of distribution divided by body weight, V/BW (L/kg). We also determined the covariant effects on clearance derived from estimated creatinine clearance, CLCr (mL/min), hepatic function parameters, and serum albumin, ALB (g/dL). In the study, we derived the equations: CL=0.214+0.397·(CLCr/80) ·(1+1.78·3)/(1+1.78·ALB), and V/BW=1.98. CL was shown to consist of a constant and a term proportional to CLCr and inversely proportional to ALB. A simulation was performed based on various initial loading dose of 400mg, 10mg/kg ≤400mg, or 10mg/kg b.i.d., and maintenance doses of 200 or 400 mg/day depending on renal function. The trough concentrations at 24, 48, and 72 h after the start of treatment were computed for 10,000 subjects using the population pharmacokinetic parameters determined herein. In the simulation, the concentrations at 72 h after the first dose were calculated to be 11.2,11.0, and 12.4mg/L, respectively, and the rates of the subjects achieving therapeutic concentration, ≥10mg/L, were 66.4, 66.3, and 96.5% of subjects, respectively. These results suggest that renal function is an important factor for CL of teicoplanin. Hypo-albuminaemia, which is often induced in patients suffering from poor nutritional conditions and increases the risk of severe infection, increases CL and reduces the concentration of teicoplanin. It is possible that the loading dose of 10 mg/kg improves the achievement ratio for the therapeutic concentration of teicoplanin and the outcome of patients with severe infection.