Population pharmacokinetics of teicoplanin in patients with endocarditis.
Teicoplanin is a new glycopeptide antibiotic, active against aerobic and anaerobic gram-positive bacteria. The drug is intended for the treatment of systemic infections including endocarditis. In two U.S. clinical safety and efficacy trials, loading doses of 6 to 30 mg/kg doses of teicoplanin were administered initially to 197 patients, followed by once-a-day treatment of approximately the same doses over several weeks. Blood samples were collected sporadically during the study to monitor serum teicoplanin concentrations either by FPIA or microbiological assay. Nonlinear mixed-effects modeling was performed on these data to characterize the population pharmacokinetics of teicoplanin that were best described by a two-compartment model. Patient body weight, concomitant gram-positive drug treatment, and serum creatinine had significant influences on systemic clearance (CL) of the glycopeptide. In addition, body weight affected the volume of distribution of the central compartment (Vc). Other demographic factors such as age, gender, etc., had no effects. The FPIA assay method was more precise than the microbiological assay.
Yu
D K
DK
U.S. Pharmacokinetics Department, Hoechst Marion Roussel, Inc., Kansas City, Missouri 64137, USA.
Nordbrock
E
E
Hutcheson
S J
SJ
Lewis
E W
EW
Sullivan
W
W
Bhargava
V O
VO
Weir
S J
SJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D004697:Endocarditis, Bacterial / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D017334:Teicoplanin / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D017334:Teicoplanin