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

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

Eur J Clin Pharmacol. 2015 Jun;71(6):707-14

Authors: Worboys PD, Wong SL, Barriere SL

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 [PubMed - in process]