Lopinavir

spinqualitylabelsall models Lopinavir, better known as Kaletra, (2q5k) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Better Known as: Kaletra Marketed By: Abbott Laboratories Major Indication: Human Immunodeficiency Virus Infection Drug Class: HIV Protease Inhibitor Date of FDA Approval (Patent Expiration): 2000 (2016) 2007 Sales: $1.1 Billion Importance: Forms part of the Lopinavir & Ritonavir first-line therapy for HIV infections. Due to its low bioavilbility, it is sold as a co-formulation with Ritonavir, which is a potent CYP3A4 inhibitor. See Pharmaceutical Drugs for more information about other drugs and diseases. Mechanism of Action When HIV infects an individuals body, it directs the synthesis of several polyproteins. The maturation of the virus to its infectious form requires that these polyproteins be cleaved to their component proteins by HIV Protease. The subunits of HIV Protease come together to form a catalytic tunnel capable of binding the nascent peptides and cleaving them into their mature form. Within this tunnel lies two Asp-Thr-Gly conserved sequences, which contain the catalytic Asp residues. These catalytic Asp residues carry out the hydrolytic cleavage of the polyprotein. Indinavir binds with great specificity to these conserved sequences within the HIV Protease tunnel, preventing the nascent polyproteins from entering. Unable to cleave the nascent proteins into their appropriate form, HIV is unable to mature and proliferate, allowing the patients immune system to fight off the infection more easily. Drug Resistance The biggest difficulty with treating HIV is the rapidity at which it mutates and becomes resistant to treatments. To view a comprehensive and interactive analysis of the mutations which confer drug resistance to HIV Protease, See: HIV Protease Inhibitor Resistance Profile

Pharmacokinetics

HIV Protease Inhibitor Human Immunodeficiency Virus Parameter HIV Protease Ritonavir Pharmaceutical Drugs HIV HIV Protease HIV Lopinavir HIV Protease HIV Protease Inhibitor Resistance Profile Nelfinavir Tmax (hr) 4.4 ~3 1.5 3.7 .98 1.5-4 2 .5 2-4 3.1 Cmax (ng/ml) 13120 14600 8100 2297 4901 4820 11.9 2730 ~4393 4701 Bioavailability (%) -- -- 65 4 -- -- -- -- 68 20-80 Protein Binding (%) 99 >99 61 98 90 90 99 95 86 98 T1/2 (hr) 4.8 4.2 1.2 4.5 5.5 7.7 6.1 29.4 5.3 3.3 AUC (ng/ml/hr) 128100 46500 20900 13467 11999 35000 117600 4746 ~26045 31906 Clearance (L/h) ~8.4 32.4 49.5 36.7 56.8 84.4 1.7 32.8 13.6 37.3 Dosage (mg) 600 600 800 1000 600 1400 280 400 400 1250 Metabolism Hepatic (CYP3A4 & CYP2C19) Hepatic (CYP3A4) Hepatic (CYP3A4) Hepatic (CYP3A4 & CYP3A5) Hepatic (CYP3A4) Hepatic (CYP3A4) Hepatic (CYP3A4) Hepatic (CYP3A4) Hepatic (CYP3A4) Hepatic (CYP3A4) For Pharmacokinetic Data References, See: References

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