Lopinavir

Structural formula
General
Non-proprietary name	Lopinavir
other names	(2 S ) - N - [(2 S , 4 S , 5 S ) -5 - {[(2,6-dimethylphenoxy) acetyl] amino} -4-hydroxy-1,6-diphenyl-2-hexanyl] - 3-methyl-2- (2-oxotetrahydro-1 (2 H ) -pyrimidinyl) butanamide ( IUPAC )
Molecular formula	C 37 H 48 N 4 O 5
External identifiers / databases
CAS number 192725-17-0 PubChem 92727 ChemSpider 83706 DrugBank DB01601 Wikidata Q422585
Drug information
ATC code	J05 AE06
Drug class	Antiviral
Mechanism of action	HIV protease inhibitor
properties
Molar mass	628.81 g · mol -1
Melting point	124-127 ° C
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS hazard labeling no classification available
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Lopinavir (LPV / r) is a drug that is used as a protease inhibitor to treat HIV infection. This HIV protease inhibitor is sold in combination with ritonavir by the manufacturer Abbott - AbbVie under the trade name Kaletra . Approval by the EU Commission took place in March 2001. For the market in third world countries, the same combination of active ingredients with the name Aluvia was registered after an initial refusal by the manufacturer . (See Abbott - Critique of the Company )

indication

The combination of active ingredients in Kaletra is approved for both adults and children over two years of age. Clinical tests showed a higher effectiveness compared to the comparison substances nelfinavir and indinavir .

pharmacology

The HIV protease inhibitor lopinavir inhibits the further processing of the viral precursor proteins newly formed by the HIV virus into functional structural proteins and enzymes and thus the replication of the virus .

Combination with ritonavir

Lopinavir is very rapidly metabolized in the human body by the cytochrome P450 system . Administration of this substance alone would have no therapeutic effect due to the insufficient concentration that can be achieved in the blood plasma . Therefore, the active ingredient is only administered in a fixed combination with ritonavir, a drug from the same group. The task of this second protease inhibitor is to block the degradation mechanism for lopinavir, i.e. the cytochrome P450 monooxygenases. This means that a sufficient concentration of lopinavir is available in the body to effectively inhibit the HIV proteases. The benefit of this strategy is a significant reduction in the dose and thus the number of tablets for the patient.

unwanted effects

In accordance with experience with the other representatives of protease inhibitors, gastrointestinal disorders such as diarrhea, abdominal pain, and abnormal stool often occur during therapy with lopinavir . CNS or skin reactions, as well as pancreatitis and rhabdomyolysis, are rarely observed . Under certain circumstances, there may be increased laboratory values ​​( cholesterol and triglycerides ).

Patients with structural heart disease , cardiac arrhythmia, a poorly supplied heart ( ischemia ) or cardiomyopathies should use Kaletra with caution.

Interactions

Due to the mechanism of action and the underlying strategy of the active ingredient combination of Kaletra , there are many impairments of the organism and interactions with other drugs. The inhibition of the enzymes of the cytochrome P450 system in the liver not only leads to an increase in the concentration of the protease inhibitors in the organism, but inevitably also to a greater bioavailability and thus a stronger effect of other drugs that are eliminated via the same mechanism ( e.g. benzodiazepines , antiarrhythmics , ergot alkaloids ). In addition, this enzyme system can be inhibited or promoted in its effect by a wide variety of influences, is not equally active in every person and is most likely gender and ethno-specific. This fact makes not only the combination Kaletra , but the entire group of protease inhibitors drugs that are subject to particularly careful therapy monitoring by experienced physicians. A risk-benefit balance is most appropriate with regard to multiple medication.

Miscellaneous

On June 25, 2005, Brazil threatened to ignore the patent for the anti- AIDS drug Kaletra and to approve generic drugs if the manufacturer did not cut prices within 10 days. It is known that 600,000 Brazilians are infected with HIV.

Thailand decided in March 2007 to suspend the patent for Kaletra after negotiations with the manufacturer Abbott Laboratories failed. Abbott had offered to reduce the price from 1,850 euros to 1,700 euros (annual dose). A generic can be offered for around 760 euros. The government justifies the suspension of the patent with an emergency regulation from an agreement of the World Trade Organization . 500,000 people have AIDS in Thailand. 20,000 receive Kaletra .

A combination of lopinavir and ritonavir is being tested in clinical trials against COVID-19 . They are part of the World Health Organization's “Solidarity” study, which began in March 2020, and some of them are tested in beta interferon . They are also part of the “Discovery” large-scale study that began at the end of March 2020, in the context of which remdesivir and hydroxychloroquine are to be compared with the previous treatment on more than 3000 Covid-19 patients in eight European countries. Kaletra is one of a series of drugs, of which the German Federal Ministry of Health will purchase millions of packs from April 2020 to be used as an alternative in the event of severe courses against Covid-19.

Web links

• Illustrations of Lopinavir and how it works

Individual evidence

1. ↑ ^{a b c} Entry on lopinavir. In: Römpp Online . Georg Thieme Verlag, accessed on July 13, 2019.
2. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
3. ^ FDA Issues Safety Labeling Changes for Kaletra, April 10, 2009, Medscape Today .
4. ↑ AIDS drugs: US pharmaceutical company declares war on Thailand. In: Spiegel Online . March 15, 2007, accessed June 29, 2015 . 
5. ↑ Anja Martini, Christian Drosten : Coronavirus Update. (PDF) Episode 22. In: ndr.de. Norddeutscher Rundfunk, March 26, 2020, p. 4 f. , accessed on March 27, 2020 . 
6. ↑ Julia Koch: Insane speed . In: Der Spiegel . No. 14 , 2020, p. 106 ( online - March 28, 2020 ).
7. ↑ Kazuhiro Nogi: What can the flu drug Avigan, which the federal government is buying, do? In: spiegel.de. April 2, 2020, accessed April 2, 2020 . 

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !