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Antimicrobial Agents and Chemotherapy, July 2006, p. 2309-2315, Vol. 50, No. 7
0066-4804/06/$08.00+0     doi:10.1128/AAC.01313-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Pharmacokinetics of Telbivudine in Healthy Subjects and Absence of Drug Interaction with Lamivudine or Adefovir Dipivoxil

Xiao-Jian Zhou,* Barbara A. Fielman, Deborah M. Lloyd, George C. Chao, and Nathaniel A. Brown

Idenix Pharmaceuticals, Inc., Cambridge, Massachusetts

Received 6 October 2005/ Returned for modification 3 December 2005/ Accepted 20 April 2006

Two phase I studies were conducted to assess the plasma pharmacokinetics of telbivudine and potential drug-drug interactions between telbivudine (200 or 600 mg/day) and lamivudine (100 mg/day) or adefovir dipivoxil (10 mg/day) in healthy subjects. Study drugs were administered orally. The pharmacokinetics of telbivudine were characterized by rapid absorption with biphasic disposition. The maximum concentrations in plasma (Cmax) were reached at median times ranging from 2.5 to 3.0 h after dosing. Mean single-dose Cmax and area under the plasma concentration-time curve from time zero to infinity (AUC0-{infty}) were 1.1 and 2.9 µg/ml and 7.4 and 21.8 µg · h/ml for the 200- and 600-mg telbivudine doses, respectively. Steady state was reached after daily dosing for 5 to 7 days. The mean steady-state Cmax and area under the plasma concentration-time curve over the dosing interval (AUC{tau}) were 1.2 and 3.4 µg/ml and 8.9 and 27.5 µg · h/ml for the 200- and 600-mg telbivudine repeat doses, respectively. The steady-state AUC{tau} of telbivudine was 23 to 57% higher than the single-dose values. Concomitant lamivudine or adefovir dipivoxil did not appear to significantly alter the steady-state plasma pharmacokinetics of telbivudine; the geometric mean ratios and associated 90% confidence interval (CI) for the AUC{tau} of telbivudine alone versus in combination were 106.3% (92.0 to 122.8%) and 98.6% (86.4 to 112.5%) when coadministered with lamivudine and adefovir dipivoxil, respectively. Similarly, the steady-state plasma pharmacokinetics of lamivudine or adefovir were not markedly affected by the coadministration of telbivudine; the geometric mean ratios and associated 90% CI, alone versus in combination with telbivudine, were 99.0% (87.1 to 112.4%) and 92.2% (84.0 to 101.1%), respectively, for the lamivudine and adefovir AUC{tau} values. Moreover, the combination regimens studied were well tolerated in all subjects. The results from these studies provide pharmacologic support for combination therapy or therapy switching involving telbivudine, lamivudine, and adefovir dipivoxil for the treatment of chronic hepatitis B virus infection.

* Corresponding author. Mailing address: Idenix Pharmaceuticals, Inc., 60 Hampshire St., Cambridge, MA 02139. Phone: (617) 995-9805. Fax: (617) 995-9817. E-mail: zhou.xiao-jian{at}idenix.com.

Antimicrobial Agents and Chemotherapy, July 2006, p. 2309-2315, Vol. 50, No. 7
0066-4804/06/$08.00+0     doi:10.1128/AAC.01313-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Scarsi, K. K., Darin, K. M. (2009). Chronic Hepatitis B Infection: Principles of Therapy. Journal of Pharmacy Practice 22: 359-387 [Abstract]  
  • Zhou, X.-J., Ke, J., Sallas, W. M., Farrell, C., Mayers, D. L., Pentikis, H. S. (2009). Population Pharmacokinetics of Telbivudine and Determination of Dose Adjustment for Patients With Renal Impairment. J Clin Pharmacol 49: 725-734 [Abstract] [Full Text]  
  • Bridges, E. G., Selden, J. R., Luo, S. (2008). Nonclinical Safety Profile of Telbivudine, a Novel Potent Antiviral Agent for Treatment of Hepatitis B. Antimicrob. Agents Chemother. 52: 2521-2528 [Abstract] [Full Text]  
  • Dusheiko, G, Antonakopoulos, N (2008). Current treatment of hepatitis B. Gut 57: 105-124 [Full Text]  
  • Zhou, X.-J., Swan, S., Smith, W. B., Marbury, T. C., Dubuc-Patrick, G., Chao, G. C., Brown, N. A. (2007). Pharmacokinetics of Telbivudine in Subjects with Various Degrees of Renal Impairment. Antimicrob. Agents Chemother. 51: 4231-4235 [Abstract] [Full Text]  
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