Lack of effect of moderate hepatic impairment on the pharmacokinetics of telavancin.
OBJECTIVE
To evaluate the pharmacokinetics of the lipoglycopeptide antibiotic, telavancin, in patients with moderate hepatic impairment compared with healthy controls.


METHODS
Phase I, open-label, single-dose, matched-control, pilot study.


METHODS
Clinical research unit.


METHODS
Eight adults with moderate hepatic impairment (Child-Pugh class B) and eight age-, sex-, and weight-matched healthy control subjects.


METHODS
All participants received a single 1-hour intravenous infusion of telavancin 10 mg/kg.


RESULTS
Plasma samples were collected for pharmacokinetic analysis before the infusion and 1, 2, 4, 6, 8, 12, 24, 36, 48, and 72 hours after the start of the infusion. Concentrations of telavancin and the most prevalent of several minor hydroxylated metabolites, THRX-651540, were assayed with a validated liquid chromatography-tandem mass spectrometry technique. Telavancin binding to plasma proteins was determined in a preinfusion sample by using equilibrium dialysis. Pharmacokinetic parameters for telavancin and THRX-651540 were generally similar between the hepatic impairment and control groups. The mean maximum plasma concentration was 21% lower in patients with hepatic impairment than in controls, which was a statistically (analysis of variance, p<0.05), but not clinically, significant difference. There were no other statistically significant between-group differences. Adverse events were few and mild.


CONCLUSIONS
No apparent differences were observed in the pharmacokinetic disposition of telavancin in patients with hepatic impairment compared with healthy controls in this pilot study. Thus, adjustment of the standard telavancin dosage regimen does not appear to be required in patients with mild-to-moderate hepatic impairment.
Goldberg
Michael R
MR
Department of Clinical Pharmacology, Theravance, Inc., South San Francisco, California 94080, USA.
Wong
Shekman L
SL
Shaw
Jeng-Pyng
JP
Kitt
Michael M
MM
Barriere
Steven L
SL
D000293:Adolescent; D000328:Adult; D000368:Aged; D000617:Aminoglycosides / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics*; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D005260:Female; D048550:Hepatic Insufficiency / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007262:Infusions, Intravenous; D000077427:Lipoglycopeptides; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D053719:Tandem Mass Spectrometry; D055815:Young Adult
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000077427:Lipoglycopeptides; C548132:THRX 651540; C487637:telavancin