Single-dose pharmacokinetics of teicoplanin during hemodialysis therapy using high-flux polysulfone membranes.
Teicoplanin is a new glycopeptide antibiotic with potent activity against Gram-positive bacteria. It has been considered to be non-dialyzable due to its high molecular weight (1875-1891 d) and high protein binding (89%). Therefore, a reduced dose was recommended for patients on hemodialysis therapy, with the loading dose being followed by a considerably lower maintenance dose and/or extension of the interval between doses. The present study was performed to evaluate the pharmacokinetics of teicoplanin during hemodialysis therapy using high flux membranes. The pharmacokinetic parameters of teicoplanin were studied in 15 patients with chronic renal failure on hemodialysis. A high flux polysulfone membrane (ultrafiltration coefficient of 40 ml/h/mmHg) was used. Teicoplanin was administered at a dosage of 10 mg.kg-1 body weight in 100 ml isotonic saline solution during the first 10 minutes of hemodialysis therapy. Pharmacokinetic analysis was performed using a three compartment analysis. After a single dose of teicoplanin plasma peak levels were 26.4 +/- 12.0 micrograms/mL (mean +/- SD) after 30 minutes. Teicoplanin concentrations rapidly declined to a nadir of 6.1 +/- 2.5 micrograms/mL at the end of the 3.5-hour session dialysis. Extracorporeal clearance was 39.7 +/- 24.5 mL/min. Removal of 19.3 +/- 7.7% of the drug was estimated if infused during hemodialysis. T 1/2 alpha were 0.37 +/- 0.25 hrs, t 1/2 beta 20.1 +/- 7.1 hrs, and t 1/2 gamma 549.7 +/- 210.5 hrs. We conclude that teicoplanin levels are reduced to a subtherapeutic range during one single high-flux dialysis session if the drug is administered during hemodialysis. Thus, in contrast to previous suggestions relevant amounts of teicoplanin are removed during hemodialysis and thus teicoplanin cannot be viewed as non-dialyzable drug. We recommend obligatory drug monitoring to achieve therapeutic plasma concentrations.
Thalhammer
F
F
Department of Infectious Diseases and Chemotherapy, University of Vienna, Austria.
Rosenkranz
A R
AR
Burgmann
H
H
Graninger
W
W
Hollenstein
U
U
Schenk
P
P
Thalhammer-Scherrer
R
R
Traindl
O
O
Hörl
W H
WH
Breyer
S
S
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001672:Biocompatible Materials; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy; D007688:Kidneys, Artificial; D008297:Male; D008567:Membranes, Artificial; D008657:Metabolic Clearance Rate / Q000502:physiology; D008875:Middle Aged; D011108:Polymers; D013450:Sulfones; D017334:Teicoplanin / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D008567:Membranes, Artificial; D011108:Polymers; D013450:Sulfones; C017662:polysulfone P 1700; D017334:Teicoplanin