Teicoplanin pharmacokinetics in patients with chronic renal failure.

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.