title: Area under the curve predictions of dalbavancin, a new lipoglycopeptide agent, using the end of intravenous infusion concentration data point by regression analyses such as linear, log-linear and power models.
abstract: 1. Dalbavancin, a lipoglycopeptide, is approved for treating gram-positive bacterial infections. Area under plasma concentration versus time curve (AUCinf) of dalbavancin is a key parameter and AUCinf/MIC ratio is a critical pharmacodynamic marker. 2. Using end of intravenous infusion concentration (i.e. Cmax) Cmaxversus AUCinfrelationship for dalbavancin was established by regression analyses (i.e. linear, log-log, log-linear and power models) using 21 pairs of subject data. 3. The predictions of the AUCinfwere performed using published Cmaxdata by application of regression equations. The quotient of observed/predicted values rendered fold difference. The mean absolute error (MAE)/root mean square error (RMSE) and correlation coefficient (r) were used in the assessment. 4. MAE and RMSE values for the various models were comparable. The Cmaxversus AUCinfexhibited excellent correlation (r > 0.9488). The internal data evaluation showed narrow confinement (0.84-1.14-fold difference) with a RMSE < 10.3%. The external data evaluation showed that the models predicted AUCinfwith a RMSE of 3.02-27.46% with fold difference largely contained within 0.64-1.48. 5. Regardless of the regression models, a single time point strategy of using Cmax(i.e. end of 30-min infusion) is amenable as a prospective tool for predicting AUCinfof dalbavancin in patients.
authors.affiliation: a Drug Metabolism and Pharmacokinetics, Jubilant Biosys Ltd , Bangalore , Karnataka , India.
authors.forename: Ravi Kanth
authors.initials: RK
authors.lastname: Bhamidipati
authors.affiliation: b Department of Pharmaceutics , University of Florida , FL , USA , and.
authors.forename: Muzeeb
authors.initials: M
authors.lastname: Syed
authors.affiliation: a Drug Metabolism and Pharmacokinetics, Jubilant Biosys Ltd , Bangalore , Karnataka , India.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Mullangi
authors.affiliation: c Suramus Bio, Drug Development , Bangalore , Karnataka , India.
authors.forename: Nuggehally
authors.initials: N
authors.lastname: Srinivas
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism*; D019540:Area Under Curve; D007262:Infusions, Intravenous; D011446:Prospective Studies; D012044:Regression Analysis; D017334:Teicoplanin / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D017334:Teicoplanin; C469289:dalbavancin
keywords: AUC; dalbavancin; regression analysis