Alacovir Mechanism of Action

abacavir + lamivudine




Full Prescribing Info
Pharmacology: Pharmacodynamics: Mechanism of action: Abacavir: Abacavir is a carbocyclic synthetic nucleoside analog. Abacavir is converted by cellular enzymes to the active metabolite, carbovir triphosphate (CBV-TP), an analog of deoxyguanosine-5'-triphosphate (dGTP). CBV-TP inhibits the activity of HIV-1 reverse transcriptase by competing with the native substrate dGTP and by its incorporation into viral DNA. The lack of a 3'-OH group in the incorporated nucleotide analogue prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated. CBV-TP is a weak inhibitor of cellular DNA polymerases alpha, beta, and gamma.
Lamivudine: Lamivudine is a synthetic nucleoside analog. Intracellularly, lamivudine is phosphorylated to its active 5'-triphosphate metabolite, lamivudine triphosphate (3TC-TP). The principal mode of action of 3TC-TP is inhibition of reverse transcriptase via DNA chain termination after incorporation of the nucleotide analogue. 3TC-TP are weak inhibitors of cellular DNA polymerases alpha, beta, and gamma.
Dose/concentration/time-pharmacodynamic response relationship: Data is not available.
Pharmacokinetics: Absorption: Abacavir: Following oral administration, abacavir is rapidly absorbed and extensively distributed. After oral administration of a single dose of abacavir 600 mg, peak plasma concentration (Cmax) was 4.26±1.19 mcg/mL and area under the curve (AUC) was 11.95±2.51 mcg·h/mL. The oral bioavailability of abacavir is 86±25%.
Lamivudine: Following oral administration, lamivudine is rapidly absorbed and extensively distributed. After multiple-dose oral administration of lamivudine 300 mg one daily for 7 days, steady-state Cmax (Cmax,ss) was 2.04±0.54 mcg/mL and the 24-hour steady-state AUC (AUC24,ss) was 8.87±1.83 mcg·h/mL. The oral bioavailability of lamivudine is 86±16%.
Distribution: Abacavir: The apparent volume of distribution of abacavir is 0.86±0.15 L/kg. Binding of abacavir to human plasma proteins is approximately 50% and was independent of concentration. Abacavir readily distributes into erythrocytes.
Lamivudine: The apparent volume of distribution of lamivudine is 1.3±0.4 L/kg. Binding to plasma protein is low.
Metabolism: Abacavir: The primary routes of abacavir are metabolism by alcohol dehydrogenase to form the 5'-carboxylic acid and glucuronyl transferase to form the 5'-glucuronide.
Lamivudine: Metabolism of lamivudine is a minor route of elimination. The only known metabolite is the trans-sulfoxide metabolite (approximately 5% of an oral dose after 12 hours).
Elimination: Abacavir: The systemic and renal clearances of abacavir are 0.8±0.24 and 0.007±0.008 L/h/kg, respectively. Its elimination half-life is 1.45±0.32 hours.
Lamivudine: The systemic and renal clearances of lamivudine are 0.33±0.06 and 0.22±0.06 L/h/kg, respectively. Its elimination half-life approximately ranges from 5 to 7 hours. Approximately 70% of an intravenous dose of lamivudine is recovered as unchanged drug in the urine.
Special populations: Renal function impairment: Lamivudine requires dose adjustment in the presence of renal insufficiency; Alacovir tablet is not recommended for use in patients with CrCl less than 50 mL/min.
Hepatic function impairment: Abacavir is contraindicated in patients with moderate to severe hepatic impairment and dose reduction is required in patients with mild hepatic impairment. Because Alacovir tablet is a fixed-dose combination and cannot be dose adjusted, Alacovir tablet is contraindicated for patients with hepatic impairment.
Toxicology: Mechanism of toxicity: Data is not available.
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