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Absorption
Bioavailability of tablet is 100% relative to oral solution. T max is between 0.5 and 1.5 h. Steady state achieved after 6 to 10 days. For 0.5 mg dose, C max was 4.2 ng/mL and C trough was 0.3 ng/mL; for 1 mg dose, C max was 8.2 ng/mL and C trough was 0.5 ng/mL. Administration with food decreases C max 44% to 46% and AUC 18% to 20%.
Distribution
Approximately 13% protein bound. Vd in excess of total body water suggesting extensive distribution into tissues.
Metabolism
No oxidative or acetylated metabolites found. Minor amounts of phase 2 metabolites (glucuronide, sulfate conjugates) noted.
Elimination
Terminal elimination t ½ is 128 to 149 h; accumulation t ½ approximately 24 h. Eliminated predominantly by kidney (both glomerular filtration and tubular secretion), with 62% to 73% of dose recovered in the urine.
Special Populations
Renal Function Impairment
C max and AUC increased in patients with moderate to severe renal impairment or with end-stage renal disease. Dose reduction recommended for patients with Ccr less than 50 mL/min.
Elderly
AUC 29.3% greater in elderly subjects; most likely secondary to decrease in renal function. Base dose adjustment of entecavir on renal function of patient and not on age.
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