Pharmacokinetics of teicoplanin in renal failure

Abstract

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.

Pharmacokinetics of teicoplanin in critically ill patients with various degrees of renal impairment

“…This paper differs from previous reports of teicoplanin pharmacokinetics (9,11,12) in several ways: (i) the antibiotic determination was done by the SPERA method, (ii) the pharmacological evaluation was made during days 4 and 5 of therapy, (iii) the study population consisted of patients with various degrees of renal impairment, and (iv) the enrolled patients were admitted to intensive-care units with lifethreatening diseases requiring multiple drug infusions. It is 50.…”

“…For 10 patients, concentrations in serum were determined on day 10, at 1 and 24 h postdose, with the same regimen. The levels in serum were 29 ± 8 and 7.6 ± 3 ,ug -ml-' compared w-ith 31.5 -+-8 and 9.5 ± 3.5 ,ug ml-' on day 4 …”

Teicoplanin pharmacokinetics in patients undergoing continuous ambulatory peritoneal dialysis after intravenous and intraperitoneal dosing

“…In addition, excellent tolerability and bioavailability after intramuscular injection have been reported (4, 12, 20, 21, 24-26, 30, 33). Renal excretion of unchanged teicoplanin is a major route of drug elimination, and preliminary dosage adjustment recommendations for patients with renal impairment have been published (1,6,7,17,27). However, few data exist on the pharmacokinetics of teicoplanin in patients receiving continuous ambulatory peritoneal dialysis (CAPD) (3,17,27).…”

Composition specification of teicoplanin based on its estimated relative bioavailability

“…In 1990, Bernareggi et al published 12 mean (n ¼ 5) plasma levels of active subcomponents from 0 to 72 h and their triexponential equations. In contrast, Falcoz et al 13 did not publish raw plasma levels, but reported the corresponding AUC 120 0 of each subcomponent in normorenal patients. Hanada et al 14,15 reported a total analytical composition of teicoplanin and a population pharmacokinetic study of A2-2 to A2-5.…”