Lopinavir

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (12:56, 11 January 2024) (edit) (undo)
 
(2 intermediate revisions not shown.)
Line 1: Line 1:
-
<applet load="" size="480" color="" frame="true" spin="on" Scene ="Lopinavir/Lopinavir/1" align="right" caption="Lopinavir, better known as Kaletra, ([[2q5k]])"/>
+
<StructureSection load='' size='340' side='right' caption='Lopinavir, better known as Kaletra, ([[2q5k]])' scene='Lopinavir/Lopinavir/1'>
===Better Known as: Kaletra===
===Better Known as: Kaletra===
* Marketed By: Abbott Laboratories<br />
* Marketed By: Abbott Laboratories<br />
Line 7: Line 7:
* 2007 Sales: $1.1 Billion
* 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.
* 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.
-
* The following is a list of Pharmacokinetic Parameters. See: [[Pharmaceutical Drugs]] for more information
+
* See [[Pharmaceutical Drugs]] for more information about other drugs and diseases.
===Mechanism of Action===
===Mechanism of Action===
Line 14: Line 14:
===Drug Resistance===
===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]]
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]]
-
 
+
</StructureSection>
===Pharmacokinetics===
===Pharmacokinetics===
-
{| class="wikitable" border="1" width="52%" style="text-align:center"
+
<table style="background: cellspacing="0px" align="" cellpadding="0px" width="42%">
-
|-
+
<tr>
-
! colspan="12" align="center"| HIV Protease Inhibitor [[Pharmaceutical_Drugs#Pharmacokinetics_Translated|Pharmacokinetics]]<ref>PMID:20400409</ref><ref>Ferry et al, United States Patent US6147095, Pharmacia & Upjohn Company.</ref><ref>L. Veronese et al. Single-Dose Pharmacokinetics of Amprenavir, a Human Immunodeficiency Virus Type 1 Protease Inhibitor, in Subjects with Normal or Impaired Hepatic Function. Antimicrob Agents Chemother. 2000 April; 44(4): 821–826.</ref><ref>J. Ford, et al. Intracellular and Plasma Pharmacokinetics of Saquinavir-Ritonavir, Administered at 1,600/100 Milligrams Once Daily in Human Immunodeficiency Virus-Infected Patients. Antimicrob Agents Chemother. 2004 July; 48(7): 2388–2393.</ref><ref>PMID:10620574</ref><ref>PMID:16086644</ref><ref>PMID:19131522</ref><ref>PMID: 10952482</ref><ref>PMID:16338276</ref><ref>PMID:19729375</ref><ref>PMID:12668574</ref><ref>PMID:17255144</ref><ref>PMID:10858338</ref>
+
<td style="width:100%; vertical-align:top;border-width:0px; border-style:inset">
-
|-
+
<div style="height:100%; width: 100%">
-
! Parameter
+
{{:HIV Protease Inhibitor Pharmacokinetics}}
-
! [[Ritonavir]]
+
</div>
-
! [[Tipranavir]]
+
</td>
-
! [[Indinavir]]
+
</tr>
-
! [[Saquinavir]]
+
</table>
-
! [[Amprenavir]]
+
-
! [[Fosamprenavir]]
+
-
! [[Lopinavir]]
+
-
! [[Darunavir]]
+
-
! [[Atazanavir]]
+
-
! [[Nelfinavir]]
+
-
|-
+
-
! [[Pharmaceutical_Drugs#Tmax|T<sub>max</sub>]] (hr)
+
-
! 4.4
+
-
! ~3
+
-
! 1.5
+
-
! 3.7
+
-
! .98
+
-
! 1.5-4
+
-
! 2
+
-
! .5
+
-
! 2-4
+
-
! 3.1
+
-
|-
+
-
! [[Pharmaceutical_Drugs#Cmax|C<sub>max</sub>]] (ng/ml)
+
-
! 13120
+
-
! 14600
+
-
! 8100
+
-
! 2297
+
-
! 4901
+
-
! 4820
+
-
! 11.9
+
-
! 2730
+
-
! ~4393
+
-
! 4701
+
-
|-
+
-
! [[Pharmaceutical_Drugs#Bioavailability_.28F.29|Bioavailability]] (%)
+
-
! --
+
-
! --
+
-
! 65
+
-
! 4
+
-
! --
+
-
! --
+
-
! --
+
-
! --
+
-
! 68
+
-
! 20-80
+
-
|-
+
-
! [[Pharmaceutical_Drugs#Protein_Binding|Protein Binding]] (%)
+
-
! 99
+
-
! >99
+
-
! 61
+
-
! 98
+
-
! 90
+
-
! 90
+
-
! 99
+
-
! 95
+
-
! 86
+
-
! 98
+
-
|-
+
-
! [[Pharmaceutical_Drugs#Half_Life_.28T1.2F2.29|T<sub>1/2</sub>]] (hr)
+
-
! 4.8
+
-
! 4.2
+
-
! 1.2
+
-
! 4.5
+
-
! 5.5
+
-
! 7.7
+
-
! 6.1
+
-
! 29.4
+
-
! 5.3
+
-
! 3.3
+
-
|-
+
-
! [[Pharmaceutical_Drugs#Area_Under_the_Curve_.28AUC.29|AUC]] (ng/ml/hr)
+
-
! 128100
+
-
! 46500
+
-
! 20900
+
-
! 13467
+
-
! 11999
+
-
! 35000
+
-
! 117600
+
-
! 4746
+
-
! ~26045
+
-
! 31906
+
-
|-
+
-
! [[Pharmaceutical_Drugs#Clearance_.28Cl.29|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)
+
-
|}
+
===References===
===References===

Current revision

Lopinavir, better known as Kaletra, (2q5k)

Drag the structure with the mouse to rotate

Pharmacokinetics

HIV Protease Inhibitor Pharmacokinetics
Parameter Ritonavir Tipranavir Indinavir Saquinavir Amprenavir Fosamprenavir Lopinavir Darunavir Atazanavir 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

References

  1. ↑ Spinelli S, Liu QZ, Alzari PM, Hirel PH, Poljak RJ. The three-dimensional structure of the aspartyl protease from the HIV-1 isolate BRU. Biochimie. 1991 Nov;73(11):1391-6. PMID:1799632
  2. ↑ Reddy GS, Ali A, Nalam MN, Anjum SG, Cao H, Nathans RS, Schiffer CA, Rana TM. Design and synthesis of HIV-1 protease inhibitors incorporating oxazolidinones as P2/P2' ligands in pseudosymmetric dipeptide isosteres. J Med Chem. 2007 Sep 6;50(18):4316-28. Epub 2007 Aug 16. PMID:17696512 doi:10.1021/jm070284z


Proteopedia Page Contributors and Editors (what is this?)

David Canner, Alexander Berchansky

Retrieved from "http://52.214.119.220/wiki/index.php/Lopinavir"
Personal tools