Researchers have now discovered that the concentration of the two drugs — Lopinavir and hydroxychloroquine (HCQ) — in the lungs of Covid-19 patients is not sufficient to fight the virus.
Lopinavir is a drug against HIV while hydroxychloroquine (HCQ) is used to treat malaria and rheumatism. Both drugs were regarded as the potential agents in the fight against the coronavirus (SARS-CoV-2).
“Previous studies have shown the inhibition of drug metabolism by systemic inflammation, we had the rationale to investigate the effect of inflammation on lopinavir and hydroxychloroquine plasma levels,” said study author Catia Marzolini from the University of Basel in Switzerland.
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The research team included 92 patients in their stud and prospectively monitored lopinavir plasma levels in Covid-19 patients. For the findings, published in the journal Antimicrobial Agents and Chemotherapy, a Covid-19 patient cohort was established to monitor a range of diagnostic means and potential treatments for coronavirus, including the off-label use of hydroxychloroquine and lopinavir/ritonavir.
The study showed that lopinavir plasma levels were more than two to threefold higher than typically observed in HIV patients.
According to the researchers, hydroxychloroquine levels were with normal range. There was a significant correlation between the inflammation marker levels in the blood and lopinavir plasma levels.
When the inflammation was blocked with the Interleukin-6 inhibitor Tocilizumab, lopinavir plasma levels were significantly lower than the ones in patients without Tozulizumab treatment.
These results clearly indicate that drug metabolism enzymes (cytochrome P450 3A) are inhibited by systemic inflammation.
“Caution is advised when prescribing CYP3A4 substrates such as Lopinavir/ritonavir or any other drug with a narrow therapeutic index to Covid-19 patients because of the risk of elevated drug levels and related toxicities,” the authors stated.
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Importantly, from the lopinavir and hydroxychloroquine concentrations in the plasma, the study group calculated the corresponding concentration in the lung compartment – the anatomic site of SARS-CoV-2 infection.
The results strongly suggest that it is unlikely that both drugs reach sufficient concentrations to inhibit virus replication in the lung.
On July 5, The World Health Organization (WHO) announced that it was discontinuing hydroxychloroquine and lopinavir/ritonavir arms for its ‘Solidarity Trial’, citing little or no reduction in the mortality of hospitalised Covid-19 patients. (IANS)