Pharmacokinetics of telbivudine in subjects with various degrees of renal impairment

Xiao Jian Zhou, Suzanne Swan, William Smith, Thomas C. Marbury, Gloria Dubuc-Patrick, George C. Chao, Nathaniel A. Brown

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

This study evaluates the effect of renal impairment on the pharmacokinetics of telbivudine. Thirty-six subjects were assigned, on the basis of creatinine clearance (CLCR), 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 (CLR), and urinary excretion of telbivudine decreased as renal function deteriorated. A linear relationship was established between CL R and CLCR. 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.

Original languageEnglish (US)
Pages (from-to)4231-4235
Number of pages5
JournalAntimicrobial Agents and Chemotherapy
Volume51
Issue number12
DOIs
StatePublished - Dec 1 2007

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Pharmacokinetics
Kidney
Chronic Kidney Failure
telbivudine
Renal Dialysis
Creatinine
Demography
Urine

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Zhou, X. J., Swan, S., Smith, W., Marbury, T. C., Dubuc-Patrick, G., Chao, G. C., & Brown, N. A. (2007). Pharmacokinetics of telbivudine in subjects with various degrees of renal impairment. Antimicrobial Agents and Chemotherapy, 51(12), 4231-4235. https://doi.org/10.1128/AAC.00557-07

Pharmacokinetics of telbivudine in subjects with various degrees of renal impairment. / Zhou, Xiao Jian; Swan, Suzanne; Smith, William; Marbury, Thomas C.; Dubuc-Patrick, Gloria; Chao, George C.; Brown, Nathaniel A.

In: Antimicrobial Agents and Chemotherapy, Vol. 51, No. 12, 01.12.2007, p. 4231-4235.

Research output: Contribution to journalArticle

Zhou, XJ, Swan, S, Smith, W, Marbury, TC, Dubuc-Patrick, G, Chao, GC & Brown, NA 2007, 'Pharmacokinetics of telbivudine in subjects with various degrees of renal impairment', Antimicrobial Agents and Chemotherapy, vol. 51, no. 12, pp. 4231-4235. https://doi.org/10.1128/AAC.00557-07
Zhou, Xiao Jian ; Swan, Suzanne ; Smith, William ; Marbury, Thomas C. ; Dubuc-Patrick, Gloria ; Chao, George C. ; Brown, Nathaniel A. / Pharmacokinetics of telbivudine in subjects with various degrees of renal impairment. In: Antimicrobial Agents and Chemotherapy. 2007 ; Vol. 51, No. 12. pp. 4231-4235.
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