Teicoplanin Pharmacokinetics in Patients with Chronic Renal Failure

Abstract

The pharmacokinetic profile of teicoplanin, a new glycopeptide antibiotic active against Gram-positive aerobic and anaerobic bacteria, was studied in 5 healthy male volunteers and 29 adult patients with various degrees of renal impairment, given a single 3 mg/kg intravenous dose. Teicoplanin was assayed in plasma and urine specimens by a microbiological method. Pharmacokinetic parameters for teicoplanin were estimated both by a 3-compartment open pharmacokinetic model and by non-compartmental analysis. Elimination half-life increased with the decrease in creatinine clearance and mean values ranged from 41 hours in volunteers to 163 hours in anuric patients. Renal failure did not affect either the volume of distribution of the central compartment (mean approximately 0.09 L/kg) or the steady-state volume of distribution (mean approximately 0.9 L/kg). Both total and renal clearance decreased with severity of disease, particularly the latter, while non-renal clearance was unaffected by renal failure. Average values were from 19 to 6 ml/min for total clearance and from 12 to 0.4 ml/min for renal clearance. There was a linear correlation between the total clearance of teicoplanin and creatinine clearance, as well as between renal clearance and creatinine clearance. The total urinary excretion of active teicoplanin averaged 65% of the administered dose in normal subjects, but was significantly reduced in the presence of renal insufficiency. Guidelines for administration of teicoplanin in patients with renal failure are given.

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

“…The mean elimination half-life of 266 h after i.v. administration noted in this study is prolonged compared with values of 149 to 163 h noted in previous studies in patients with end-stage renal disease (1,27) and similar to that noted recently by Brouard et al (377 h) (3). These previous investigators utilized a shorter sampling duration which may have contributed to this difference (1,27).…”

“…administration noted in this study is prolonged compared with values of 149 to 163 h noted in previous studies in patients with end-stage renal disease (1,27) and similar to that noted recently by Brouard et al (377 h) (3). These previous investigators utilized a shorter sampling duration which may have contributed to this difference (1,27). These values contrast sharply with mean elimination half-life values of 44 to 61 h noted in healthy volunteers with normal renal function (4,26,30).…”

“…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).…”

Influence of arterio‐venous haemofiltration on teicoplanin elimination.

“…Less than 1% of the administered dose was recovered in seven patients, between 1.8 and 3.8% in three patients, and 7% in one patient. [2]. However, in this trial, the sampling duration was much longer, 168 h and should be considered as the exact one.…”

Improvement of Predictivity of Teicoplanin Serum Trough Concentrations at Steady State Calculated by Vancomycin Pharmacokinetic Parameter

“…7) TEIC clearance decreased with renal failure, a response attributed to the reduction of urinary excretion of TEIC in patients with chronic renal impairment. 18) PEVCM and PETEIC showed a low positive correlation (R 2 ＝0.271, p＝0.0173).The Cockcroft and Gualt equation is the most commonly used in clinical practice to estimate drug clearance. As shown in Table 1, creatinine clearance is a covariate of interpatient variability for VCM and TEIC.…”