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Lopinavir

Chemical compound

Summary

Chemical compound

| Drugs.com =

| elimination_half-life = 5 to 6 hours

Lopinavir is an antiretroviral of the protease inhibitor class. It is used against HIV infections as a fixed-dose combination with another protease inhibitor, ritonavir (lopinavir/ritonavir).

It was patented in 1995 and approved for medical use in 2000. Considered now as second-line therapy in the West, it is still prescribed in LMIC, especially among children living with HIV. Lopinavir and ritonavir can be taken as a tablet or an oral solution, a preferred option in children. In the early stages of COVID-19 pandemics, lopinavir was repurposed against the SARS-CoV-2 virus in the hope of disturbing its protease activity.

Side effects

Side effects, interactions, and contraindications have only been evaluated in the drug combination lopinavir/ritonavir. They include nausea, vomiting, and stomach aches.

Pharmacology

Lopinavir is highly bound to plasma proteins (98–99%).

Reports are contradictory regarding lopinavir penetration into the cerebrospinal fluid (CSF). Anecdotal reports state that lopinavir cannot be detected in the CSF; however, a study of paired CSF-plasma samples from 26 patients receiving lopinavir/ritonavir found lopinavir CSF levels above the IC50 in 77% of samples.

Research

A 2014 study indicates that lopinavir is effective against the human papilloma virus (HPV). The study used the equivalent of one tablet twice a day applied topically to the cervices of women with high-grade and low-grade precancerous conditions. After three months of treatment, 82.6% of the women who had high-grade disease had normal cervical conditions, confirmed by smears and biopsies. Lopinavir has been shown to impair protein synthesis via AMP-activated protein kinase (AMPK) and eEF2 kinase (eEF2K) activation, a mechanism that is similar to the antiviral effect of protein phosphatase 1 inhibitors.

Lopinavir was found to inhibit MERS-CoV replication in the low-micromolar range in cell cultures. In 2020, lopinavir/ritonavir was found not to work in severe COVID-19. In this trial the medication was started typically around 13 days after the start of symptoms.

References

References

  1. "FDA Approved Drug Products: Kaletra".
  2. (2006). "Analogue-based Drug Discovery". John Wiley & Sons.
  3. (2021). "Systems and Clinical Pharmacology of COVID-19 Therapeutic Candidates: A Clinical and Translational Medicine Perspective". Journal of Pharmaceutical Sciences.
  4. [http://www.rxabbott.com/pdf/kaletratabpi.pdf Kaletra (lopinavir/ritonavir) capsules; (lopinavir/ritonavir) oral solution. Prescribing information. April 2009]
  5. (June 2005). "Lopinavir concentrations in cerebrospinal fluid exceed the 50% inhibitory concentration for HIV". AIDS.
  6. link. (22 March 2014 University of Manchester, 17 February 2014.)
  7. (2021). "Protein phosphatase 1 regulates Human Cytomegalovirus protein translation by restraining AMPK signaling". Frontiers in Microbiology.
  8. (November 2014). "1E7-03, a low MW compound targeting host protein phosphatase-1, inhibits HIV-1 transcription". British Journal of Pharmacology.
  9. (August 2014). "Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture". Antimicrobial Agents and Chemotherapy.
  10. (May 2020). "A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19". The New England Journal of Medicine.
Wikipedia Source

This article was imported from Wikipedia and is available under the Creative Commons Attribution-ShareAlike 4.0 License. Content has been adapted to SurfDoc format. Original contributors can be found on the article history page.

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