Pharmacokinetics of teicoplanin upon multiple-dose intravenous administration of 3, 12, and 30 milligrams per kilogram of body weight to healthy male volunteers

Abstract

Teicoplanin pharmacokinetics were evaluated after multiple-dose intravenous administration to healthy male volunteers by using a randomized, double-blind, parallel design. Doses of 3, 12, or 30 mg of teicoplanin per kg of body weight were administered every 24 h for 14 days as 60-min constant-rate intravenous infusions. Blood and urine samples were collected over 21 days and analyzed by a microbiological assay. Twenty-three subjects were included in the pharmacokinetic analysis. The median pharmacokinetic parameters upon multiple-dose intravenous administration of 3, 12, and 30 mg/kg included steady-state volumes of distribution of 0.94, 0.77, and 0.68 liter/kg; total clearances of 11.9, 12.0, and 13.2 ml/h/kg; and terminal disposition half-lives of 143, 166, and 96 h, respectively. Renal clearance accounted for approximately 95% of total clearance. No dose-related differences existed for teicoplanin total or renal clearance. The steady-state volume of distribution decreased significantly with increasing doses. As a result of the decrease in the volume of distribution, the terminal disposition half-life at 30 mg/kg was significantly decreased. However, the decreases in the volume of distribution and terminal disposition half-life are of limited clinical importance, since steady-state trough concentrations in serum increase in proportion to dose. Combined results of all multiple-dose studies with similar durations of sample collection indicate no dose-related differences for any pharmacokinetic parameters from 3 to 12 mg/kg. As observed in the present study, no dose-related differences exist for teicoplanin total and renal clearances from 3 to 30 mg/kg. However, at 30 mg/kg, a significant decrease in the steady-state volume of distribution is observed. As a consequence of the reduction in the volume of distribution at 30 mg/kg with no change in clearance, the terminal disposition half-life is decreased.Teicoplanin is a new glycopeptide antibiotic, chemically related to vancomycin and ristocetin. It is active against aerobic and anaerobic gram-positive bacteria (4,8,12,15). Its effect on susceptible bacteria is bactericidal, and like vancomycin, it interferes with cell wall synthesis (18).In earlier studies, the pharmacokinetics of teicoplanin were determined on the basis of plasma concentration-time profiles obtained over 3 to 4 days (22, 24). A review of these studies has recently been published (16). In more recent studies, the duration of sample collection has been extended up to 3 weeks, resulting in a more complete characterization of the serum concentration-time profile (1,11,14,21). As a result of the increase in the duration of sample collection, teicoplanin total clearance was found to be slightly less and the volumes of distribution and terminal disposition half-life were found to be greater than previously reported. Results from these more recent studies indicate that the pharmacokinetics of teicoplanin upon multiple-dose intravenous administration are linear over the range of 3 to 12 mg/kg of body wei...

Population pharmacokinetic study of teicoplanin in severely neutropenic patients

“…100 to 150 h). However, plasma or urine has to be collected for 21 days to ensure a precise determination of the parameters of the terminal elimination phase (5,23). In our study, fitting a triexponential model to the data was not statistically superior to on July 4, 2020 by guest http://aac.asm.org/ using a biexponential model, probably because teicoplanin treatment was discontinued after 2 weeks for most subjects ( Table 2).…”

“…In most recent studies of teicoplanin pharmacokinetics, the disposition of teicoplanin has been described by a triexponential model (23), indicating a very long terminal half-life (ca. 100 to 150 h).…”

Daptomycin or teicoplanin in combination with gentamicin for treatment of experimental endocarditis due to a highly glycopeptide-resistant isolate of Enterococcus faecium

“…To evaluate whether the synergistic effect observed in killing curves between teicoplanin, which was used at an inhibitory concentration, and gentamicin could be relevant in vivo, HiD teicoplanin was evaluated. Such a regimen, which provided very high peak and trough levels in serum, would not be readily recommendable for humans, because it has previously been reported to induce adverse reactions in healthy volunteers (6,19). Its poor efficacy in rabbits, even when used in combination with gentamicin, might be explained by (i) the high degree of protein binding of the drug, as suggested by the killing curves, which showed a lack of the bactericidal effect observed with teicoplanin at VOL.…”

Exploration of optimal teicoplanin dosage based on pharmacokinetic parameters for the treatment of intensive care unit patients infected with methicillin-resistant Staphylococcus aureus

“…Currently, just four drugs-teicoplanin (TEC), vancomycin (VAN), linezolid (LZD) and arbekacin (ABK)-are used to treat MRSA infection in Japan. Because of its reduced nephrotoxicity [1] and its longer elimination half-life [2] compared with the other three drugs, TEC is increasingly being used to treat MRSA infections in Japan.…”