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 < 0.001). The cumulative urinary excretion of unchanged total teicoplanin was decreased (50, 21, and 5% of the given dose for groups I to 3) and the terminal half-life was enhanced -(62, 96, and I11 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 paanameters 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.

The accuracy of methods for measurement of creatinine in plasma, urine and dialysate is of great importance in continuous ambulatory peritoneal dialysis (CAPD) patients, to assess the adequacy of CAPD (creatinine clearance) and to monitor the nutritional status (creatinine kinetic lean body mass). The methods most widely employed for creatinine determination are Jaffe's reaction and the enzymatic method, however these techniques may suffer from glucose interference, particularly for dialysate. We compared creatinine values obtained by Jaffe's reaction, the enzymatic method and high pressure liquid chromatography (HPLC) for three creatinine calibration curves prepared in three dialysis solutions with various concentrations of glucose and for plasma, urine and dialysate of 40 CAPD patients. High values of intercept of creatinine calibration curves were observed only with Jaffe's reaction and the enzymatic method in dialysis solutions. In plasma, urine and dialysate, creatinine values obtained by HPLC were always found to be lower than those measured by the other two methods. Concerning creatinine measurement in plasma and urine, Jaffe's reaction and the enzymatic method appeared equivalent. However it must be noted that, in dialysates, the enzymatic method may have glucose interference, and the use of a correcting factor for glucose with Jaffe's reaction is convenient. Nevertheless HPLC remains a method of reference. It is concluded that, for the CAPD patient, follow-up by creatinine kinetic lean body mass or creatinine clearance is possible provided that the same creatinine assay method is used in all biological fluids.

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