Pharmacokinetics of intravenous telavancin in healthy subjects with varying degrees of renal impairment

• Published in: European journal of clinical pharmacology Vol. 71; no. 6; pp. 707 - 714
• Main Authors: Worboys, Philip D., Wong, Shekman L., Barriere, Steven L.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.06.2015; Springer Nature B.V
• Subjects: Aged; Aminoglycosides - administration & dosage; Aminoglycosides - pharmacokinetics; Area Under Curve; Biomedical and Life Sciences; Biomedicine; Female; Half-Life; Healthy Volunteers; Humans; Kidney diseases; Kidney Failure, Chronic - metabolism; Kidney Failure, Chronic - physiopathology; Male; Middle Aged; Pharmacokinetics and Disposition; Pharmacology; Pharmacology/Toxicology; Renal Dialysis - methods; Lipoglycopeptide; Hydroxypropylbetadex; Telavancin; Renal impairment; Pharmacokinetics
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-015-1847-6

Purpose We evaluated the effect of renal impairment (RI) on the pharmacokinetics of telavancin and hydroxypropylbetadex (excipient in the telavancin drug product). Methods Adults with normal, mild, moderate or severe RI or end-stage renal disease (ESRD) receiving haemodialysis were included in two open-label, phase I studies of single-dose telavancin at 7.5 mg/kg (study A, n  = 29) or 10 mg/kg (study B, n  = 43). Pharmacokinetic analysis of telavancin and hydroxypropylbetadex plasma concentration versus time was performed in these subjects. Results The results in studies A and B were similar: telavancin systemic exposure (area under the concentration–time curve from 0 to infinity [AUC 0–∞ ]) increased with RI. Telavancin half-life ( h , mean ± SD) increased in subjects with severe RI compared with subjects with normal renal function from 6.9 ± 0.6 in study A and 6.5 ± 0.9 in study B to 14.5 ± 1.3 and 11.8 ± 6.7, respectively. Conversely, clearance (ml/h/kg, mean ± SD) decreased in subjects with severe RI compared with subjects with normal renal function from 13.7 ± 2.1 in study A and 17.0 ± 3.2 in study B to 6.18 ± 0.63 and 6.5 ± 1.5, respectively. Systemic exposures for hydroxypropylbetadex also increased with severity of RI. Conclusions Results from two independent phase 1 studies suggest that dose adjustment of telavancin is required in subjects with varying degrees of RI.