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Pharmacology: Pharmacodynamics: Entecavir, a guanosine nucleoside analog, is an antiviral agent that is active against human hepatitis B virus (HBV). The drug undergoes phosphorylation by cellular enzymes to form its active metabolite, entecavir triphosphate. By competing with the natural substrate deoxyguanosine triphosphate, entecavir triphosphate inhibits activities of HBV DNA polymerase (reverse transcriptase) including base priming, reverse transcription of the negative strand from the pregenomic messenger RNA, and synthesis of the positive strand of HBV DNA.
Pharmacokinetics: Absorption: Following multiple daily doses ranging from 0.1 to 1 mg, Cmax and area under the curve (AUC) at steady state increased in proportion to dose. Steady state was achieved after 6 to 10 days of once-daily administration, with approximately 2-fold accumulation.
Oral administration of entecavir with meal resulted in delay in absorption and a decrease in AUC.
Distribution: Binding of entecavir to human serum proteins in vitro was approximately 13%. Based on the pharmacokinetic profile of entecavir after oral dosing, the estimated apparent volume of distribution is in excess of total body water, suggesting that entecavir is extensively distributed into tissues.
Metabolism/Excretion: Entecavir is excreted principally in urine via glomerular filtration and tubular secretion. Entecavir is not a substrate for and does not inhibit or induce cytochrome P-450 (CYP) isoenzymes.
