Dược Động Học :
▧ Absorption :
The approximate oral bioavailability of adefovir from HEPSERA is 59%. When a single oral 10 mg dose is given to chronic hepatitis B patients, the peak plasma concentration (Cmax) of adefovir was 18.4 ± 6.26 ng/mL. This occurred between 0.58 - 4 hours post dose (Tmax). The adefovir area under the plasma concentration-time curve (AUC0–∞) was 220 ± 70.0 ng∙h/mL. Food does not affect the exposure of adeforvir.
▧ Volume of Distribution :
* 392 ± 75 mL/kg [Vd at steady state, intravenous administration of 1.0 mg/kg/day]
* 352 ± 9 mL/kg [Vd at steady state, intravenous administration of 3.0 mg/kg/day]
▧ Protein binding :
≤4% over the adefovir concentration range of 0.1 to 25 μg/mL
▧ Metabolism :
Following oral administration, adefovir dipivoxil is rapidly converted to adefovir. 45% of the dose is recovered as adefovir in the urine over 24 hours at steady state following 10 mg oral doses. Adefovir is not a substrate of the cytochrome P450 enzymes.
▧ Route of Elimination :
Adefovir is renally excreted by a combination of glomerular filtration and active tubular secretion.
▧ Half Life :
Plasma adefovir concentrations declined in a biexponential manner with a terminal elimination half-life of 7.48 ± 1.65 hours.
▧ Clearance :
* 469 ± 99.0 mL/min [Patients with Unimpaired renal Function receiving a 10 mg single dose]
* 356 ± 85.6 mL/min [Patients with mild renal impairement receiving a 10 mg single dose]
* 237 ± 118 mL/min [Patients with moderate renal impairement receiving a 10 mg single dose]
* 91.7 ± 51.3 mL/min [Patients with severe renal impairement receiving a 10 mg single dose]