Telavancin pharmacokinetics in patients with chronic kidney disease receiving haemodialysis.

Abstract

BACKGROUND:

Telavancin is a lipoglycopeptide antibiotic with limited pharmacokinetic data to guide drug dosing in patients receiving haemodialysis.

OBJECTIVES:

This study characterized telavancin pharmacokinetics in patients receiving haemodialysis.

PATIENTS AND METHODS:

This was a Phase IV, prospective, open-label, single-centre, crossover pharmacokinetic study (ClinicalTrials.gov: NCT02392208). Eight subjects with end-stage kidney disease requiring maintenance haemodialysis (mean ± SD: 47 ± 20 years, 69.5 ± 17.1 kg) received 5 mg/kg telavancin IV 3 h before starting a 3.5 hour haemodialysis treatment with a high-permeability haemodialyser (haemodialysis period). After a 14 day washout period, a second 5 mg/kg dose was administered post-haemodialysis (control period). Telavancin plasma concentrations were measured over a 2 day period after each dose and non-compartmental pharmacokinetic analyses were performed.

RESULTS:

The geometric mean (GM) of telavancin overall clearance was 11.2 mL/h/kg (intrinsic clearance and dialytic clearance) in the haemodialysis period and 5.9 mL/h/kg (off-haemodialysis clearance) in the control period [GM ratio (GMR) = 1.89; 90% CI: 1.70-2.10; P < 0.01]. The GM t½ was 13.1 h when haemodialysis occurred 3 h post-dosing in the haemodialysis period but extended to 20.9 h with post-haemodialysis dosing in the control period (GMR = 0.63; 90% CI: 0.54-0.73; P < 0.01). The GM of telavancin plasma concentrations removed by haemodialysis was 27.7%. The GMR of peak plasma concentration and volume of distribution of the haemodialysis period and the control period were 0.88 (90% CI: 0.79-0.98; P = 0.08) and 1.17 (90% CI: 1.05-1.30; P = 0.048), respectively.

CONCLUSIONS:

Haemodialysis with high-permeability haemodialysers removes telavancin considerably (∼⅓ of body load). Telavancin 5 mg/kg every 48 h post-haemodialysis dosing is recommended, but dose adjustments may be warranted if haemodialysis starts within 3 h of telavancin administration.

• Authors: Katherine N Gharibian, Susan J Lewis, Michael Heung, Jonathan H Segal, Noha N Salama, Bruce A Mueller
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 77 Issue 1 Pg. 174-180 (12 24 2021) ISSN: 1460-2091 [Electronic] England
• PMID: 34613416 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Aminoglycosides
• Lipoglycopeptides
• telavancin

Topics

• Aminoglycosides
• Humans
• Kidney Failure, Chronic (drug therapy, therapy)
• Lipoglycopeptides (therapeutic use)
• Prospective Studies
• Renal Dialysis
• Renal Insufficiency, Chronic