Pharmacokinetics of teicoplanin in renal failure

By using a highly specific chromatographic technique, the effect of renal failure on the pharmacokinetics of the six main components of teicoplanin, taken individually or as a whole, was assessed for over 120 h after administration of a 3-mg/kg intravenous dose to healthy volunteers (group 1, n = 6) and to noninfected patients with moderate (group 2, n = 6) or severe (group 3, n = 7) renal failure. In subjects with normal renal function, total teicoplanin was mainly excreted in urine and its concentrations in plasma could be adequately fitted to a three-compartment model. Renal failure did not affect the model or the distribution of teicoplanin but strongly decreased its renal clearance (9.3, 3.2, and 0.6 ml/h per kg, respectively, for the three groups of subjects), in close relationship with the creatinine clearance (r = 0.973, n = 18, P less than 0.001). The cumulative urinary excretion of unchanged total teicoplanin was decreased (50, 21, and 5% of the given dose for groups 1 to 3) and the terminal half-life was enhanced (62, 96, and 111 h for groups 1 to 3) by renal impairment. The relative behavior of the six major components was only slightly affected by renal failure. Consequently, the dosage regimen adjustment could be based on the total teicoplanin concentration, and simulations with the mean estimated pharmacokinetic parameters suggest that the 6-mg/kg daily dose, known to be effective in patients with normal renal function, could be given every 2 and 3 days in patients with moderate and severe renal insufficiency, respectively.