A Five-day Course of Ivermectin may Reduce the Duration of COVID-19 Illness: ずくなしの冷や水


A Five-day Course of Ivermectin may Reduce the Duration of COVID-19 Illness

A Five-day Course of Ivermectin may Reduce the Duration of COVID-19 Illness

We would like to thank you for sending us the letter from Dr Ajay Kumar Shukla and Dr Saurav Misra related to our article entitled “A five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness” published in the International Journal of Infectious Diseases (Ahmed et al., 2021).

This pilot study was performed to evaluate the rapidity of viral clearance and safety of a 5-day course of ivermectin or a single-dose of ivermectin + a 5-day course of doxycycline in the treatment of mild COVID-19 in adults.

The letter states that any significant antiviral activity is unlikely to achieve the dose used in our study and the resultant plasma concentration of the administered ivermectin. In response to the letter we intend to make few comments.

We agree with Shukla and Misra, that in vitro studies showed antiviral activities of ivermectin in such a high plasma concentration which cannot be achieved through therapeutic dose in vivo. In this connection, firstly, we like to state that in vitro and in vivo studies of same drug may differ in various aspects.

Viruses are known to have high rates of replication and therefore, one day dose of ivermectin, is unlikely to have sufficient effect since half life is around 20 hours (González Canga et al., 2008). To maintain an effective concentration of ivermectin in the body we decided to give ivermectin single dose for 5 days.

The highest dose of ivermectin that we have used in our study is 12 mg (200 μg/kg) once daily for 5 consecutive days which showed significantly shorter time of viral clearance. Virological clearance was earlier in the 5-day ivermectin treatment arm when compared to the placebo group (9.7 days vs 12.7 days; p = 0.02), but this was not the case for the ivermectin + doxycycline arm (11.5 days; p = 0.27). Similar to this, clinical trial with the 3-day once daily dose of 400 μg/kg oral ivermectin on dengue patients has been proved to be safe and accelerated clearance of nonstructural protein 1 of dengue virus (Suputtamongkol et al., 2021).

In response to Shukla and others’ comment on other retrospective studies that showed no improvement in microbiological and virological clearance, we like to state that pooled analysis of 6 studies of ivermectin on COVID-19, which includes our studies showed that ivermectin administration significantly shortened the time to negative COVID -19 RT-PCR results (p = 0.007) (Hariyanto et al., 2021).

Besides, we like to state that ivermectin is a multifaced medication with anti-viral as well as anti-inflamatory and anticancerous properties. Studies of ivermectin have reported potential immunemodulatory functions of the drug, which have been hypothesized to be beneficial for COVID-19 infection (Zhang et al., 2008, Ci et al., 2009, DiNicolantonio et al., 2020). We cannot rule out the effect of immunomodulatory function of ivermectin that could be present in vivo and play synergistic role with antiviral properties of the medicine.

At last, we agree with the WHO recommendation that Shukla and others mentioned in their letter. As mentioned in the ‘Discussion’ section, we also think that a larger randomized controlled clinical trial of ivermectin treatment is warranted to validate these important findings.

Funding Source: The study was funded by the Beximco Pharmaceuticals Ltd. (BPL). icddr,b also acknowledges the governments of Bangladesh, Canada, Sweden and the UK for providing institutional support.

International Journal of Infectious Diseasesに掲載された「A five-day course of ibermectin for the treatment of COVID-19 may reduce the duration of illness」と題した論文に関連するAjay Kumar Shukla博士とSaurav Misra博士からの手紙をお送りいただき、感謝申し上げます(Ahmedら、2021年)。



我々はShuklaとMisraの意見に同意します。in vitroの研究では、生体内の治療用量では達成できないような高い血漿濃度でイベルメクチンの抗ウイルス活性が示されました。これに関連して、まず最初に、同じ薬剤のin vitroとin vivoの研究は様々な面で異なる可能性があることを述べたいと思います。

ウイルスは複製速度が速いことが知られており、半減期が約20時間であることから、イベルメクチンを1日で投与しても十分な効果は期待できません(González Canga et al., 2008)。体内のイベルメクチンの有効濃度を維持するために、イベルメクチンの単回投与を5日間行うことにした。

今回の研究で使用したイベルメクチンの最高用量は12mg(200μg/kg)を1日1回、5日間連続で投与したところ、ウイルスクリアランスの時間が有意に短くなりました。5日間のイベルメクチン投与群では、プラセボ群と比較してウイルスクリアランスが早かったが(9.7日 vs 12.7日、p = 0.02)、イベルメクチン+ドキシサイクリン投与群ではそうではなかった(11.5日、p = 0.27)。 これと同様に、デング熱患者に対してイベルメクチン400μg/kgを1日1回3日間経口投与した臨床試験では、安全性が高く、デング熱ウイルスの非構造タンパク質1のクリアランスが促進されることが証明されています(Suputtamongkolら、2021年)。

Shuklaらが微生物学的およびウイルス学的なクリアランスの改善が見られなかった他のレトロスペクティブ研究についてコメントしたことに対し、我々の研究を含むCOVID-19に対するイベルメクチンの6つの研究のプール解析では、イベルメクチン投与によりCOVID -19のRT-PCR結果が陰性になるまでの時間が有意に短縮されたことを述べたいと思います(p = 0.007)(Hariyanto et al., 2021)。



資金提供者 本研究は、Beximco Pharmaceuticals Ltd.(BPL)から資金提供を受けています。(icddr,bは、バングラデシュ政府、カナダ政府、スウェーデン政府、英国政府からの組織的支援にも謝意を表します。

posted by ZUKUNASHI at 17:01| Comment(0) | Covid19
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