Population Pharmacokinetics of Telbivudine and Determination of Dose Adjustment for Patients With Renal Impairment

Telbivudine is a new nucleoside analog indicated for the treatment of chronic hepatitis B infection. A population pharmacokinetic model was developed based on data pooled from 16 early phase studies in 363 healthy participants and patients. Telbivudine was administered as single and/or multiple dose...

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Bibliographic Details
Published in:Journal of clinical pharmacology 2009-06, Vol.49 (6), p.725-734
Main Authors: Zhou, Xiao-Jian, Ke, June, Sallas, William M., Farrell, Colm, Mayers, Douglas L., Pentikis, Helen S.
Format: Article
Language:English
Subjects:
Adult
Aged
Antiviral Agents - administration & dosage
Antiviral Agents - pharmacokinetics
Biological Availability
Female
hepatitis B
Humans
Kidney Diseases - metabolism
Male
Middle Aged
Models, Biological
Nucleosides - administration & dosage
Nucleosides - pharmacokinetics
population pharmacokinetics
Pyrimidinones - administration & dosage
Pyrimidinones - pharmacokinetics
renal impairment
Telbivudine
Thymidine - analogs & derivatives
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Summary:Telbivudine is a new nucleoside analog indicated for the treatment of chronic hepatitis B infection. A population pharmacokinetic model was developed based on data pooled from 16 early phase studies in 363 healthy participants and patients. Telbivudine was administered as single and/or multiple doses of 25 to 1800 mg daily for up to 28 days. A 2‐compartment model with first‐order input and lag time provided the best fit to the data. A final model was built with identified covariates, including creatinine clearance on plasma clearance, dose and race on bioavailability fraction, and body weight on central volume of distribution. The final model was applied to simulate steady‐state exposure for patients with impaired renal function for various dosing regimens. Results from these simulation analyses support that in patients with moderate to severe renal impairment or end‐stage renal disease, reduced daily doses of telbivudine could be an alternative to interval adjustment to achieve exposure comparable to patients with normal renal function or mild renal impairment treated with the full clinical dose.
ISSN:0091-2700
1552-4604
DOI:10.1177/0091270009333555