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Eur J Clin Pharmacol. 2015 Jun;71(6):707-714. doi: 10.1007/s00228-015-1847-6. Epub 2015 May 5.

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

Author information

1
Theravance Biopharma US, Inc., 901 Gateway Boulevard, South San Francisco, CA, 94080, USA. pworboys@theravance.com.
2
AbbVie Biotherapeutics Corp., Redwood City, CA, 94063, USA.
3
Theravance Biopharma US, Inc., 901 Gateway Boulevard, South San Francisco, CA, 94080, USA.

Abstract

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 [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.

PMID:
25939708
PMCID:
PMC4430595
DOI:
10.1007/s00228-015-1847-6
[Indexed for MEDLINE]
Free PMC Article

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