This Article Full Text Full Text (PDF) Other Versions of this Article: AAC.00557-07v1 51/12/4231    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zhou, X.-J. Articles by Brown, N. A. Search for Related Content PubMed PubMed Citation Articles by Zhou, X.-J. Articles by Brown, N. A.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, December 2007, p. 4231-4235, Vol. 51, No. 12
0066-4804/07/$08.00+0     doi:10.1128/AAC.00557-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Pharmacokinetics of Telbivudine in Subjects with Various Degrees of Renal Impairment

Idenix Pharmaceuticals, Inc., Cambridge, Massachusetts,¹ DaVita Clinical Research,² Hennepin County Medical Center, Minneapolis, Minnesota,³ New Orleans Center for Clinical Research, New Orleans, Louisiana,⁴ Orlando Clinical Research Center, Orlando, Florida⁵

Received 27 April 2007/ Returned for modification 22 June 2007/ Accepted 7 September 2007

This study evaluates the effect of renal impairment on the pharmacokinetics of telbivudine. Thirty-six subjects were assigned, on the basis of creatinine clearance (CL_CR), to 1 of 5 renal function groups with 6 to 8 subjects per group: normal renal function; mild, moderate, or severe renal impairment; or end-stage renal disease [ESRD] requiring hemodialysis. Subjects received a single oral dose of telbivudine at 600 mg (normal function and mild impairment), 400 mg (moderate impairment), or 200 mg (severe impairment and ESRD); plasma and/or urine samples were collected over a 48-h period for pharmacokinetic analyses. Telbivudine was well tolerated by all subjects. The pharmacokinetics of 600 mg of telbivudine were comparable for subjects with mild renal impairment and normal renal function. Likewise, for subjects with moderate to severe impairment, including ESRD, reduced doses from 200 to 400 mg produced plasma exposure similar to that for subjects with normal renal function. These results indicate that the pharmacokinetics of telbivudine were dependent on renal function, especially for subjects with moderate to severe renal impairment or ESRD. Apparent total plasma clearance, renal clearance (CL_R), and urinary excretion of telbivudine decreased as renal function deteriorated. A linear relationship was established between CL_R and CL_CR. In ESRD subjects, a routine 3.5- to 4-h hemodialysis session removed telbivudine from plasma at an extraction ratio of 45%, representing a 23% reduction in total exposure. These results suggest that while no adjustment of the telbivudine dose appears necessary for subjects with mild renal impairment, dose adjustment is warranted for those with moderate to severe renal impairment or ESRD in order to achieve optimal plasma exposure.

Published ahead of print on 17 September 2007.