Drug Groups

approved; investigational

Description

Telbivudine is a synthetic thymidine nucleoside analog with specific activity against the hepatitis B virus. Telbivudine is orally administered, with good tolerance, lack of toxicity and no dose-limiting side effects.

Indication

For the treatment of chronic hepatitis B in adult and adolescent patients ≥16 years of age with evidence of viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.

Pharmacology

Telbivudine is a synthetic thymidine nucleoside analogue with activity against hepatitis B virus (HBV). Telbivudine is the unmodified β–L enantiomer of the naturally occurring nucleoside, thymidine. It undergoes phosphorylation via interaction with cellular kinases to form the active metabolite, telbivudine 5'-triphosphate.

Toxicity

There is no information on intentional overdose of telbivudine, but one subject experienced an unintentional and asymptomatic overdose. Healthy subjects who received telbivudine doses up to 1800 mg/day for 4 days had no increase in or unexpected adverse events. A maximum tolerated dose for telbivudine has not been determined.

Affected Organisms

Biotransformation

No metabolites of telbivudine were detected following administration of [14C]–telbivudine in humans. Telbivudine is not a substrate, or inhibitor of the cytochrome P450 (CYP450) enzyme system.

Absorption

Absorbed following oral administration. Telbivudine absorption and exposure were unaffected when a single 600–mg dose was administered with a high–fat (~55 g), high–calorie (~950 kcal) meal.

Half Life

Approximately 15 hours.

Protein Binding

In vitro binding of telbivudine to human plasma proteins is low (3.3%).

Elimination

Telbivudine is eliminated primarily by urinary excretion of unchanged drug.

Clearance

* 7.6 +/- 2.9 L/h [Normal renal function (Clcr>80 mL/min)]
* 5.0 +/- 1.2 L/h [Mild renal function impairement (Clcr=50-80 mL/min)]
* 2.6 +/- 1.2 L/h [Moderate renal function impairement (Clcr=30-49 mL/min)]
* 0.7 +/- 0.4 L/h [Severe renal function impairement (Clcr<30 mL/min)]

References

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