Dược Động Học :
▧ Absorption :
Rapid and nearly complete absorption from the gastrointestinal tract following oral administration; however, because of first-pass metabolism, systemic bioavailability of zidovudine capsules and solution is approximately 65% (range, 52 to 75%). Bioavailability in neonates up to 14 days of age is approximately 89%, and it decreases to approximately 61% and 65% in neonates over 14 days of age and children 3 months to 12 years, respectively. Administration with a high-fat meal may decrease the rate and extent of absorption.
▧ Volume of Distribution :
Apparent volume of distribution, HIV-infected patients, IV administration = 1.6 ± 0.6 L/kg
▧ Protein binding :
▧ Metabolism :
Hepatic. Metabolized by glucuronide conjugation to major, inactive metabolite, 3′-azido-3′-deoxy-5′- O-beta-D-glucopyranuronosylthymidine (GZDV). UGT2B7 is the primary UGT isoform that is responsible for glucuronidation. Compared to zidovudine, GZDV's area under the curve is approximately 3-fold greater. The cytochrome P450 isozymes are responsible for the reduction of the azido moiety to form 3'-amino-3'- deoxythymidine (AMT).
▧ Route of Elimination :
As in adult patients, the major route of elimination was by metabolism to GZDV. After intravenous dosing, about 29% of the dose was excreted in the urine unchanged and about 45% of the dose was excreted as GZDV.
▧ Half Life :
Elimination half life, HIV-infected patients, IV administration = 1.1 hours (range of 0.5 - 2.9 hours)
▧ Clearance :
* 0.65 +/- 0.29 L/hr/kg [HIV-infected, Birth to 14 Days of Age]
* 1.14 +/- 0.24 L/hr/kg [HIV-infected, 14 Days to 3 Months of Age]
* 1.85 +/- 0.47 L/hr/kg [HIV-infected, 3 Months to 12 Years of Age].
The transporters, ABCB1, ABCC4, ABCC5, and ABCG2 are involved with the clearance of zidovudine.