Population pharmacokinetics of tigecycline in healthy volunteers.
Tigecycline, a novel glycylcycline, possesses broad-spectrum antimicrobial activity. A structural population pharmacokinetic model for tigecycline was developed based on data pooled from 5 phase I studies. Intravenous tigecycline was administered as single (12.5-300 mg) or multiple (25-100 mg) doses every 12 hours for up to 10 days. Three-compartment models with zero-order input and first-order elimination separately described the single- or multiple-dose full-profile data. Additional models were evaluated using a subset of the phase I data mimicking the phase II/III trial sparse-sampling scheme and dosage. A 2-compartment model best described the reduced phase I data following single or multiple doses and provided reliably accurate estimates of tigecycline AUC(0-12). This modeling supported phase II/III population pharmacokinetic model development to further determine individual patient tigecycline exposures for safety and efficacy analyses.
Van Wart
S A
SA
Cognigen Corporation, 395 Youngs Road, Buffalo, NY 14221, USA. scott.vanwart@cognigencorp.com
Cirincione
B B
BB
Ludwig
E A
EA
Meagher
A K
AK
Korth-Bradley
J M
JM
Owen
J S
JS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D017321:Clinical Trials, Phase I as Topic; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008911:Minocycline / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D008954:Models, Biological; D015337:Multicenter Studies as Topic; D000078304:Tigecycline
D000900:Anti-Bacterial Agents; D000078304:Tigecycline; D008911:Minocycline