Dalbavancin Population Pharmacokinetic Modeling and Target Attainment Analysis

被引:33
作者
Carrothers, Timothy J. [1 ]
Chittenden, Jason T. [2 ]
Critchley, Ian [3 ,4 ]
机构
[1] Allergan Plc, 5 Giralda Farms, Madison, NJ 07940 USA
[2] qPharmetra LLC, Cary, NC USA
[3] Allergan Plc, Irvine, CA USA
[4] Spero Therapeut, Cambridge, MA USA
关键词
acute bacterial skin and skin structure infection; dalbavancin; long-acting intravenous antibiotic; pharmacokinetics; target attainment; ACUTE BACTERIAL SKIN; ONCE-WEEKLY DALBAVANCIN; STAPHYLOCOCCUS-AUREUS; PHARMACODYNAMICS; THERAPY; RESISTANCE; EFFICACY; MICE;
D O I
10.1002/cpdd.695
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Dalbavancin is indicated for the treatment of acute bacterial skin and skin structure infections caused by susceptible gram-positive microorganisms. This analysis represents the update of the population pharmacokinetics (popPK) modeling and target attainment simulations performed with data from the single-dose safety and efficacy study and an unrelated but substantial revision of the preclinical pharmacokinetic/pharmacodynamic target (fAUC/MIC, free area under concentration-time curve/minimum inhibitory concentration ratio). A 3-compartment distribution model with first-order elimination provided an appropriate fit, with typical dalbavancin clearance of 0.05 L/h and total volume of distribution of similar to 15 L. Impact of intrinsic factors was modest, although statistically significant (P < .05) relationships with total clearance were found for the following covariates: creatinine clearance, weight, and albumin - dose adjustment was only indicated for severe renal impairment. Under the new nonclinical target, simulations of the popPK model projected that >99% of subjects would achieve the nonclinical target at MIC values up to and including 2 mg/L.
引用
收藏
页码:21 / 31
页数:11
相关论文
共 31 条
[1]   Dalbavancin: Quantification in human plasma and urine by a new improved high performance liquid chromatography-tandem mass spectrometry method [J].
Alebic-Kolbah, Tanja ;
Demers, Roger ;
Cojocaru, Laura .
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 2011, 879 (25) :2632-2641
[2]   Pharmacokinetics-pharmacodynamics of antimicrobial therapy: It's not just for mice anymore [J].
Ambrose, Paul G. ;
Bhavnani, Sujata M. ;
Rubino, Christopher M. ;
Louie, Arnold ;
Gumbo, Tawanda ;
Forrest, Alan ;
Drusano, George L. .
CLINICAL INFECTIOUS DISEASES, 2007, 44 (01) :79-86
[3]   In vivo pharmacodynamic activity of the glycopeptide dalbavancin [J].
Andes, David ;
Craig, William A. .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2007, 51 (05) :1633-1642
[4]   Pharmacodynamics of dalbavancin studied in an in vitro pharmacokinetic system [J].
Bowker, Karen E. ;
Noel, Alan R. ;
MacGowan, Alasdair P. .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2006, 58 (04) :802-805
[5]   Population pharmacokinetic analysis of dalbavancin, a novel lipoglycopeptide [J].
Buckwalter, M ;
Dowell, JA .
JOURNAL OF CLINICAL PHARMACOLOGY, 2005, 45 (11) :1279-1287
[6]  
CLSI, 2015, M07-A10-Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically. Approved Standard, V10th
[7]   Pharmacokinetic/pharmacodynamic parameters: Rationale for antibacterial dosing of mice and men [J].
Craig, WA .
CLINICAL INFECTIOUS DISEASES, 1998, 26 (01) :1-10
[8]   Human pharmacokinetics and rationale for once-weekly dosing of dalbavancin, a semi-synthetic glycopeptide [J].
Dorr, MB ;
Jabes, D ;
Cavaleri, M ;
Dowell, J ;
Mosconi, G ;
Malabarba, A ;
White, RJ ;
Henkel, TJ .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2005, 55 :25-30
[9]   Pharmacokinetic-pharmacodynamic modeling of dalbavancin, a novel glycopeptide antibiotic [J].
Dowell, James A. ;
Goldstein, Beth R. ;
Buckwalter, Mary ;
Stogniew, Martin ;
Damle, Bharat .
JOURNAL OF CLINICAL PHARMACOLOGY, 2008, 48 (09) :1063-1068
[10]   Antimicrobial pharmacodynamics: Critical interactions of 'bug and drug' [J].
Drusano, GL .
NATURE REVIEWS MICROBIOLOGY, 2004, 2 (04) :289-300