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Entecavir Pharmacokinetics, Safety, and Tolerability After Multiple Ascending Doses in Healthy Subjects
Author(s) -
Yan JingHe,
Bifano Marc,
Olsen Steven,
Smith Robert A.,
Zhang Duxi,
Grasela Dennis M.,
LaCreta Frank
Publication year - 2006
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270006293304
Subject(s) - pharmacokinetics , tolerability , entecavir , medicine , dosing , placebo , dose ranging study , urine , adverse effect , pharmacology , urology , double blind , hepatitis b virus , virus , alternative medicine , pathology , virology , lamivudine
A double‐blind, placebo‐controlled, multiple oral dose escalation study was conducted to investigate the pharmacokinetics, safety, and tolerability of entecavir in healthy subjects. Eight subjects were assigned to each of the 3 dose panels (0.1 mg, 0.5 mg, and 1 mg or matched placebo once daily for 14 days). Blood and urine samples were collected for pharmacokinetic analyses. Entecavir was rapidly absorbed, with peak plasma concentration occurring within 1 hour of dosing. Steady‐state plasma concentrations of entecavir were achieved by 10 days following the initial dose. At steady state, the mean area under the plasma concentration‐time curve over 1 dosing interval, increased approximately proportional to dose. Entecavir had a mean terminal half‐life ranging from 128 to 149 hours and an effective half‐life of approximately 24 hours. Elimination was predominantly through renal excretion, with mean urinary recovery ranging from 62% to 73%. Entecavir was safe and well tolerated when administered at doses ranging from 0.1 mg to 1 mg/d for 14 days.