title: A physiologically-based pharmacokinetic model for the antibiotic ertapenem.
abstract: Ertapenem is an antibiotic commonly used to treat a broad spectrum of infections, which is part of a broader class of antibiotics called carbapenem. Unlike other carbapenems, ertapenem has a longer half-life and thus only has to be administered once a day. A physiologically-based pharmacokinetic (PBPK) model was developed to investigate the uptake, distribution, and elimination of ertapenem following a single one gram dose. PBPK modeling incorporates known physiological parameters such as body weight, organ volumes, and blood flow rates in particular tissues. Furthermore, ertapenem is highly bound in human blood plasma; therefore, nonlinear binding is incorporated in the model since only the free portion of the drug can saturate tissues and, hence, is the only portion of the drug considered to be medicinally effective. Parameters in the model were estimated using a least squares inverse problem formulation with published data for blood concentrations of ertapenem for normal height, normal weight males. Finally, an uncertainty analysis of the parameter estimation and model predictions is presented.
authors.affiliation: Department of Mathematics and Statistics, East Tennessee State University, Johnson City, TN, 37614, United States. email: joynerm@etsu.edu.
authors.forename: Michele L
authors.initials: ML
authors.lastname: Joyner
authors.forename: Cammey C
authors.initials: CC
authors.lastname: Manning
authors.forename: Whitney
authors.initials: W
authors.lastname: Forbes
authors.forename: Michelle
authors.initials: M
authors.lastname: Maiden
authors.forename: Ariel N
authors.initials: AN
authors.lastname: Nikas
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D003198:Computer Simulation; D000077727:Ertapenem; D006801:Humans; D007262:Infusions, Intravenous; D007413:Intestinal Mucosa / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D009928:Organ Specificity; D014018:Tissue Distribution; D047090:beta-Lactams / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D000077727:Ertapenem