telavancin and Renal-Insufficiency

Telavancin biological activity, determined by serum titers against a reference strain of Staphylococcus aureus, was maintained in the serum of subjects with severe renal impairment or end-stage renal disease suggesting that there is no apparent effect of renal function on in vitro activity of telavancin.

Topics: Adult; Aged; Aminoglycosides; Anti-Bacterial Agents; Female; Humans; Kidney Failure, Chronic; Lipoglycopeptides; Male; Microbial Sensitivity Tests; Middle Aged; Reference Values; Renal Insufficiency; Staphylococcal Infections; Staphylococcus aureus

U.S. Food and Drug Administration (FDA) recommended telavancin dosing is based on total body weight (TBW) but lacks adjusted regimens for obese subjects with varying renal function. Our aim was to develop a physiologically based pharmacokinetic (PBPK) model of telavancin to design optimized dosing regimens for obese patients with hospital-acquired pneumonia (HAP) and varying renal function.. The PBPK model was verified using clinical pharmacokinetic (PK) data of telavancin in healthy populations with varying renal function and obese populations with normal renal function. Then, the PBPK model was applied to predict the PK in obese HAP patients with renal impairment (RI).. The fold error values of PK parameters (AUC, C. The PBPK simulation proposed that using TBW-based regimen in obesity with RI should be avoided. Dose recommendations in obesity from the PBPK model are 750 mg daily for normal renal function and mild RI, 610 mg daily for moderate RI, 530 mg daily for severe RI, and 480 mg daily for ESRD.

Topics: Adult; Aminoglycosides; Anti-Bacterial Agents; Area Under Curve; Body Weight; Computer Simulation; Healthcare-Associated Pneumonia; Humans; Lipoglycopeptides; Male; Models, Biological; Monte Carlo Method; Obesity; Renal Insufficiency