Lopinavir (ABT-378) is a peptidomimetic HIV protease inhibitor effective against HIV protease with the Val 82 mutation. It is less affected by serum protein binding compared to the structurally related drug ritonavir.

HIV protease:1.3 pM(Ki)

Administering Lopinavir (10 mg/kg, p.o.) to rats resulted in a maximum concentration (Cmax) of 0.8 μg/mL, with the drug's bioavailability being 25%.

Lopinavir is an effective inhibitor of Rh123, with an IC50 value of 1.7 mM for Caco-2 cell monolayers. It binds to mutant HIV proteases (V82A, V82T, and V82F) with Ki values of 4.9, 3.7, and 3.6 pM, respectively. At a concentration of 0.5 nM, Lopinavir inhibits the activity of wild-type HIV protease by 93%. It also inhibits HIV protease activity in MT4 cells both in the presence and absence of 50% HS, with EC50 values of 102 nM and 17 nM, respectively. In liver microsomes, Lopinavir is converted to primary metabolites M-3 and M-4, a process that is NADPH-dependent. After treating LS 180V cells with Lopinavir for 72 hours, there is a reduction in intracellular Rh123 content and induction of P-glycoprotein immunoreactive protein and mRNA levels. Lopinavir exhibits an IC50 of 9.4 nM against subtype C clone C6. When acting on human liver microsomes, Lopinavir shows an IC50 of 7.3 mM against CYP3A and exerts weak inhibition on human CYP1A2, 2B6, 2C9, 2C19, and 2D6.