Pharmacokinetics of intravenous telavancin in healthy subjects with varying degrees of renal impairment.
OBJECTIVE
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 [AUC0-∞]) 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.
Theravance Biopharma US, Inc., 901 Gateway Boulevard, South San Francisco, CA, 94080, USA. pworboys@theravance.com.
Philip D
PD
Worboys
AbbVie Biotherapeutics Corp., Redwood City, CA, 94063, USA.
Shekman L
SL
Wong
Theravance Biopharma US, Inc., 901 Gateway Boulevard, South San Francisco, CA, 94080, USA.
Steven L
SL
Barriere
D000368:Aged; D000617:Aminoglycosides / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D005260:Female; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000503:physiopathology*; D000077427:Lipoglycopeptides; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis / Q000379:methods
D000617:Aminoglycosides; D000077427:Lipoglycopeptides; C487637:telavancin