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Recently, with the arrival of the peak of the epidemic, the number of severe cases across the country has gradually increased
.
The goal of epidemic prevention and control has shifted to "maintaining health and preventing severe disease"
.
A number of experts told China Newsweek that vaccination, early intervention in antiviral drug treatment in the early stage of infection, and blood oxygen testing are effective means
to prevent severe disease and death after infection.
Early use of antiviral drugs to inhibit viral replication as soon as possible will significantly reduce cell and tissue damage, which is the key to treatment and has positive significance
for shortening the course of the disease.
Professor Zhang Fujie, director of the Clinical and Research Center for Infection of Beijing Ditan Hospital, and many other experts also mentioned that azvudine can significantly shorten the nucleic acid conversion time of mild and moderate new crown infections and effectively reduce symptoms
.
A Weibo topic #Beijing Community Hospital Can Open Azvudine# made Azvudine even more popular
.
For a time, Azvudine frequently appeared in the media hot search and became an Internet celebrity drug
.
What is Azvudine?
Azvudine is a novel nucleoside reverse transcriptase and helper protein Vif (Viral infectivity factor) dual-target inhibitor, which is an antiviral class 1.
1 innovative drug with completely independent intellectual property rights and global patents in China [1-5].
。
Approved on 20 July 2021 for the treatment of HIV-1 infected adults with high viral load
.
On July 25, 2022, the State Food and Drug Administration conditionally approved the addition of indications for the treatment of new coronavirus pneumonia for the treatment of adult patients with common COVID-19[6], marking that azvudine has become the first oral small molecule new coronary pneumonia treatment drug independently developed and patented in China
.
On August 9, 2022 and January 5, 2023, Azvudine was included in the national "Diagnosis and Treatment Plan for Novel Coronavirus Pneumonia (9th Edition)" [7] and Diagnosis and Treatment Plan for Novel Coronavirus Infection (Trial Version 10)", and entered the medical insurance settlement
.
Why use azvudine?
With the increase in the number of new crown infections, the demand for new crown drugs on the market is becoming more and more strong
.
At present, there are three main types of new crown specific drugs that have been conditionally approved for marketing in China: one is Paxlovid nematevir/ritonavir tablets developed by Pfizer in the United States, one is a domestic new crown small molecule drug, namely azvudine tablets, and the other is the newly approved new crown virus treatment drug monogravir capsules
of Merck Sharp & Dohme.
Paxlovid is not only expensive, 2980 yuan per box, but also often in short supply, and several hospitals say that Paxlovid's inventory is tight, and its price on the black market is said to have been speculated to tens of thousands
.
Paxlovid is "hard to find"
.
Monoravir capsules were only approved on December 29 and are not yet in circulation
.
In contrast, the price of azvudine is lower, the online price is 270 yuan / bottle, and it can be prescribed and purchased online, which has attracted a lot of attention
.
In terms of clinical performance, the results of the international multi-center phase III clinical study of azvudine prove its efficacy and safety
against the new coronavirus.
The results of clinical trials also show that azvudine has the effect of inhibiting the replication of the new coronavirus, accelerating the clearance of the new coronavirus, reducing symptoms and shortening the course of the disease, and the low dosage is safer
.
Mechanism of action of azvudine As a broad-spectrum RNA virus inhibitor, azvudine
can embed viral RNA in the process of new coronavirus RNA synthesis, thereby inhibiting new coronavirus replication.
Achieve the role of treating COVID-19[8].
After taking azvudine, it shows obvious thymus (lymph) homing characteristics, and its active form triphosphate is concentrated in thymus (lymph) and peripheral blood mononuclear cells, so that it can activate the immune system while removing the virus in the peripheral blood, and continuously remove the virus by slowly releasing active metabolites in the thymus (lymph), protecting the immune system and achieving the effect of "treating both the symptoms and the root cause"
。 In addition, in vivo experiments in animals have confirmed that azvudine has a good protective effect
on the lungs.
Azvudine's unique antiviral mechanism, which has an intracellular half-life of more than 120 hours, can be used clinically as a long-acting oral antiviral drug [9,10].
Azvudine Randomized Controlled Clinical Trial Study
Azvudine conducted a global multicenter randomized, double-blind, placebo-controlled clinical study for the treatment of novel coronary pneumonia in China, Brazil and Russia, evaluating the effect of azvudine compared with placebo in mild, Efficacy and safety
in the population of patients with common and moderate to severe novel coronary pneumonia.
Studies have shown that azvudine significantly reduces the viral load of patients compared with the control group, significantly shortens the time to clinical improvement, and has an overall safety and tolerability profile
.
The research on the efficacy of azvudine on
the new coronavirus has proved that azvudine has a significant therapeutic effect
in shortening the average time of nucleic acid conversion to negative in patients, the time of discharge, the duration of drug treatment and accelerating the recovery of patients.
Studies have shown that after initial exposure, peak SARS-CoV-2 load, followed by a decrease, can be observed in the respiratory tract at the onset of symptoms or in the first week of illness, suggesting the highest infectious potential before or during the first 5 days of symptom onset, so antivirals should be used early in infection, i.
e.
, at the peak of replication release after the virus enters the body, to block viral replication and disease progression
。
Early high viral replication is a feature of acute infection, and initial high viral load is associated with an increased risk of death, and studies on azvudine have shown that the higher the baseline viral load, the stronger
the viral inhibition.
Azvudine had a significantly higher viral load reduction at day 5 after treatment than in the control group
.
Additional data showed that the clinical status score improved significantly at day 7 after azvudine treatment than in the control group
.
The data showed that people with the first diagnosis of asymptomatic and mild new coronavirus infection, using azvudine within 48 hours of the first positive (1 time per day, 5 mg each time, taking to two nucleic acid turns negative with an interval of 24 hours) was less likely to be used than users, and the time to turn negative after medication could be shortened by 2 days
.
Another group of studies showed that people who were first diagnosed with asymptomatic and mild new coronavirus infection used azvudine within 48 hours and reduced the length
of hospital stay by 1.
5 days compared with no users.
For special populations, in the elderly over 60 years old who have been diagnosed with asymptomatic and mild new coronavirus infection, the use of azvudine (5 mg once a day, taken to two nucleic acid negative times with an interval of 24 hours) is less likely to be used and can shorten the negative time after medication (5 days vs 7 days).
In 13 patients in the intensive care unit, azvudine reduced time in the ICU (9 versus 14 days)
compared with other medications.
How is Azvudine used?
The main dosage form of azvudine is tablets, which are available in 1 mg and 3 mg sizes
.
The 1 mg format is used to treat adults with common COVID-19
.
Dosage: Swallow the whole tablet on an empty stomach, 5 mg once daily, the course of treatment should not exceed 14 days
.
Recommended in patients with relatively early disease course and nucleic acid positive
.
If the missed dose is short, it can be retaken as soon as possible, but if it is close to the next dose time (more than half of the interval between normal doses), you can skip the missed dose and take the drug directly at the next dose, not twice the dose
at a time.
Use of azvudine in special populations
in patients with hepatic insufficiency: azvudine has not been studied
in patients with impaired liver function 。 Patients with abnormal liver function tests (ALT and/or AST exceeding the upper limit of normal, or total bilirubin exceeding the upper limit of normal) have been excluded in clinical studies, and it is recommended that patients with mild liver damage do not need to adjust the dose, and patients with moderate to severe liver function impairment should be treated with azvudine with caution, and if necessary, it is recommended to use it under the guidance of a physician and monitor the patient's liver function
.
Medication in patients with renal insufficiency: Azvudine studies have not been conducted
in patients with renal impairment or in patients on hemodialysis 。 Clinical studies have excluded patients with renal insufficiency (glomerular filtration rate < 70 mL/min, or creatinine above the upper limit of normal), and it is recommended that patients with glomerular filtration rate ≥ 70 mL/min do not need to adjust the dose, and patients with glomerular filtration rate < 70 mL/min, or creatinine above the upper limit of normal, should be treated with azvudine with caution, if necessary, it is recommended to use it under the guidance of a physician and monitor the patient's renal function
.
Pregnant / lactating medication: there have been no studies of
pregnant and lactating medication.
Not recommended during
pregnancy and lactation.
Medication in children: Azvudine has not been studied in children and is not recommended for children
.
Medication in elderly patients: Patients older than 65 years without underlying medical conditions do not need to adjust the dose, and patients with underlying diseases need to be concerned about drug-drug interactions (DDI).
Contraindications
to Azvudine are contraindicated
for those who are allergic to azvudine or any other component of the preparation.
Azvudine drug-drug interactions
According to studies in healthy subjects, azvudine in combination with tenofovir disoproxil fumarate tablets (TDF) or efavirenz tablets (EFV) increases in vivo exposure to azvudine, However, it does not affect clinical efficacy
.
When combined with TDF, there is no significant impact on TDF and there is no need to adjust TDF usage
.
When combined with EFV, the pharmacokinetic effect
on EFV cannot be judged due to the small sample size of clinical trials.
Azvudine is a P-glycoprotein (P-gp) substrate and a weak P-gp inducer [11-12].
Based on this, it is speculated that the combination of P-gp substrates (digoxin, dabigatran etexil, colchicine) and P-gp inhibitors (eg, cyclosporine, itraconazole, voriconazole, posaconazole and other azole antifungals, ritonavir, dronedarone, amiodarone, verapamil, clarithromycin, grapefruit juice), P-gp inducers (eg, rifampicin, St.
John's wort extract) should be cautious
.
If combined use is really necessary, blood drug concentration monitoring
is carried out if necessary.
Common adverse effects
of azvudine In a phase III clinical study of azvudine in the treatment of COVID-19, azvudine orally once daily (5 mg / time) for up to 14 days, similar to the adverse reactions of the control group, no statistical differences, mostly grade 1-2, common adverse reactions (incidence ≥ 1/100 to <1/10) include: ALT, AST, PLT, GGT mildly elevated, diarrhea
。 Adverse events included respiratory failure, the phase III study of azvudine was mainly included in patients with moderate infection, respiratory failure could occur in patients with moderate infection due to the high virulence of the virus strain, there was no significant difference between azvudine and control groups (1.
27% vs.
1.
27%), and azvudine itself did not increase the risk of
respiratory failure.
Azvudine adverse reactions countermeasures
Azvudine is safe and tolerated in a single administration of 1mg~5mg in HIV-infected patients, and the adverse reactions are mild, mainly manifested as fever, dizziness, nausea, diarrhea, etc.
And all of them are reported adverse reactions of similar anti-HIV drugs currently on the market, and can return to normal
with symptomatic treatment or no treatment.
<B156> Azvudine was well tolerated, had no significant effect on liver and kidney function in people with mild and moderate infection, and adverse events returned to normal quickly and were maintained until the end of treatment [13].
； For patients with diarrhea, it is necessary to distinguish whether it is caused by drugs or the virus itself, and symptomatic drugs can be taken; Patients with respiratory failure can be treated according to the relevant treatment principles, and if there is chest tightness and hypoxia, they need to go to the hospital for further observation
.
In general, azvudine, as an oral broad-spectrum RNA virus inhibitor, can effectively inhibit the replication of the new coronavirus and achieve the effect
of treating new coronary pneumonia (COVID-19).
It has fast onset, low dosage, significant efficacy in alleviating symptoms and shortening the course of the disease, and has good overall safety and tolerability, and has good clinical application prospects and accessibility in the treatment of new coronary pneumonia
.
In the face of every sudden attack of a variant, we will "save the risk"
home diagnosis and treatment services to protect everyone's health 👇
.
The goal of epidemic prevention and control has shifted to "maintaining health and preventing severe disease"
.
A number of experts told China Newsweek that vaccination, early intervention in antiviral drug treatment in the early stage of infection, and blood oxygen testing are effective means
to prevent severe disease and death after infection.
Early use of antiviral drugs to inhibit viral replication as soon as possible will significantly reduce cell and tissue damage, which is the key to treatment and has positive significance
for shortening the course of the disease.
Professor Zhang Fujie, director of the Clinical and Research Center for Infection of Beijing Ditan Hospital, and many other experts also mentioned that azvudine can significantly shorten the nucleic acid conversion time of mild and moderate new crown infections and effectively reduce symptoms
.
A Weibo topic #Beijing Community Hospital Can Open Azvudine# made Azvudine even more popular
.
For a time, Azvudine frequently appeared in the media hot search and became an Internet celebrity drug
.
What is Azvudine?
Azvudine is a novel nucleoside reverse transcriptase and helper protein Vif (Viral infectivity factor) dual-target inhibitor, which is an antiviral class 1.
1 innovative drug with completely independent intellectual property rights and global patents in China [1-5].
。
Approved on 20 July 2021 for the treatment of HIV-1 infected adults with high viral load
.
On July 25, 2022, the State Food and Drug Administration conditionally approved the addition of indications for the treatment of new coronavirus pneumonia for the treatment of adult patients with common COVID-19[6], marking that azvudine has become the first oral small molecule new coronary pneumonia treatment drug independently developed and patented in China
.
On August 9, 2022 and January 5, 2023, Azvudine was included in the national "Diagnosis and Treatment Plan for Novel Coronavirus Pneumonia (9th Edition)" [7] and Diagnosis and Treatment Plan for Novel Coronavirus Infection (Trial Version 10)", and entered the medical insurance settlement
.
Why use azvudine?
With the increase in the number of new crown infections, the demand for new crown drugs on the market is becoming more and more strong
.
At present, there are three main types of new crown specific drugs that have been conditionally approved for marketing in China: one is Paxlovid nematevir/ritonavir tablets developed by Pfizer in the United States, one is a domestic new crown small molecule drug, namely azvudine tablets, and the other is the newly approved new crown virus treatment drug monogravir capsules
of Merck Sharp & Dohme.
Paxlovid is not only expensive, 2980 yuan per box, but also often in short supply, and several hospitals say that Paxlovid's inventory is tight, and its price on the black market is said to have been speculated to tens of thousands
.
Paxlovid is "hard to find"
.
Monoravir capsules were only approved on December 29 and are not yet in circulation
.
In contrast, the price of azvudine is lower, the online price is 270 yuan / bottle, and it can be prescribed and purchased online, which has attracted a lot of attention
.
In terms of clinical performance, the results of the international multi-center phase III clinical study of azvudine prove its efficacy and safety
against the new coronavirus.
The results of clinical trials also show that azvudine has the effect of inhibiting the replication of the new coronavirus, accelerating the clearance of the new coronavirus, reducing symptoms and shortening the course of the disease, and the low dosage is safer
.
Mechanism of action of azvudine As a broad-spectrum RNA virus inhibitor, azvudine
can embed viral RNA in the process of new coronavirus RNA synthesis, thereby inhibiting new coronavirus replication.
Achieve the role of treating COVID-19[8].
After taking azvudine, it shows obvious thymus (lymph) homing characteristics, and its active form triphosphate is concentrated in thymus (lymph) and peripheral blood mononuclear cells, so that it can activate the immune system while removing the virus in the peripheral blood, and continuously remove the virus by slowly releasing active metabolites in the thymus (lymph), protecting the immune system and achieving the effect of "treating both the symptoms and the root cause"
。 In addition, in vivo experiments in animals have confirmed that azvudine has a good protective effect
on the lungs.
Azvudine's unique antiviral mechanism, which has an intracellular half-life of more than 120 hours, can be used clinically as a long-acting oral antiviral drug [9,10].
Azvudine Randomized Controlled Clinical Trial Study
Azvudine conducted a global multicenter randomized, double-blind, placebo-controlled clinical study for the treatment of novel coronary pneumonia in China, Brazil and Russia, evaluating the effect of azvudine compared with placebo in mild, Efficacy and safety
in the population of patients with common and moderate to severe novel coronary pneumonia.
Studies have shown that azvudine significantly reduces the viral load of patients compared with the control group, significantly shortens the time to clinical improvement, and has an overall safety and tolerability profile
.
Data from clinical trials of azvudine for the treatment of novel coronary pneumonia
The research on the efficacy of azvudine on
the new coronavirus has proved that azvudine has a significant therapeutic effect
in shortening the average time of nucleic acid conversion to negative in patients, the time of discharge, the duration of drug treatment and accelerating the recovery of patients.
Studies have shown that after initial exposure, peak SARS-CoV-2 load, followed by a decrease, can be observed in the respiratory tract at the onset of symptoms or in the first week of illness, suggesting the highest infectious potential before or during the first 5 days of symptom onset, so antivirals should be used early in infection, i.
e.
, at the peak of replication release after the virus enters the body, to block viral replication and disease progression
。
Early high viral replication is a feature of acute infection, and initial high viral load is associated with an increased risk of death, and studies on azvudine have shown that the higher the baseline viral load, the stronger
the viral inhibition.
Azvudine had a significantly higher viral load reduction at day 5 after treatment than in the control group
.
Additional data showed that the clinical status score improved significantly at day 7 after azvudine treatment than in the control group
.
The data showed that people with the first diagnosis of asymptomatic and mild new coronavirus infection, using azvudine within 48 hours of the first positive (1 time per day, 5 mg each time, taking to two nucleic acid turns negative with an interval of 24 hours) was less likely to be used than users, and the time to turn negative after medication could be shortened by 2 days
.
Another group of studies showed that people who were first diagnosed with asymptomatic and mild new coronavirus infection used azvudine within 48 hours and reduced the length
of hospital stay by 1.
5 days compared with no users.
For special populations, in the elderly over 60 years old who have been diagnosed with asymptomatic and mild new coronavirus infection, the use of azvudine (5 mg once a day, taken to two nucleic acid negative times with an interval of 24 hours) is less likely to be used and can shorten the negative time after medication (5 days vs 7 days).
In 13 patients in the intensive care unit, azvudine reduced time in the ICU (9 versus 14 days)
compared with other medications.
How is Azvudine used?
The main dosage form of azvudine is tablets, which are available in 1 mg and 3 mg sizes
.
The 1 mg format is used to treat adults with common COVID-19
.
Dosage: Swallow the whole tablet on an empty stomach, 5 mg once daily, the course of treatment should not exceed 14 days
.
Recommended in patients with relatively early disease course and nucleic acid positive
.
If the missed dose is short, it can be retaken as soon as possible, but if it is close to the next dose time (more than half of the interval between normal doses), you can skip the missed dose and take the drug directly at the next dose, not twice the dose
at a time.
Use of azvudine in special populations
in patients with hepatic insufficiency: azvudine has not been studied
in patients with impaired liver function 。 Patients with abnormal liver function tests (ALT and/or AST exceeding the upper limit of normal, or total bilirubin exceeding the upper limit of normal) have been excluded in clinical studies, and it is recommended that patients with mild liver damage do not need to adjust the dose, and patients with moderate to severe liver function impairment should be treated with azvudine with caution, and if necessary, it is recommended to use it under the guidance of a physician and monitor the patient's liver function
.
Medication in patients with renal insufficiency: Azvudine studies have not been conducted
in patients with renal impairment or in patients on hemodialysis 。 Clinical studies have excluded patients with renal insufficiency (glomerular filtration rate < 70 mL/min, or creatinine above the upper limit of normal), and it is recommended that patients with glomerular filtration rate ≥ 70 mL/min do not need to adjust the dose, and patients with glomerular filtration rate < 70 mL/min, or creatinine above the upper limit of normal, should be treated with azvudine with caution, if necessary, it is recommended to use it under the guidance of a physician and monitor the patient's renal function
.
Pregnant / lactating medication: there have been no studies of
pregnant and lactating medication.
Not recommended during
pregnancy and lactation.
Medication in children: Azvudine has not been studied in children and is not recommended for children
.
Medication in elderly patients: Patients older than 65 years without underlying medical conditions do not need to adjust the dose, and patients with underlying diseases need to be concerned about drug-drug interactions (DDI).
Contraindications
to Azvudine are contraindicated
for those who are allergic to azvudine or any other component of the preparation.
Azvudine drug-drug interactions
According to studies in healthy subjects, azvudine in combination with tenofovir disoproxil fumarate tablets (TDF) or efavirenz tablets (EFV) increases in vivo exposure to azvudine, However, it does not affect clinical efficacy
.
When combined with TDF, there is no significant impact on TDF and there is no need to adjust TDF usage
.
When combined with EFV, the pharmacokinetic effect
on EFV cannot be judged due to the small sample size of clinical trials.
Azvudine is a P-glycoprotein (P-gp) substrate and a weak P-gp inducer [11-12].
Based on this, it is speculated that the combination of P-gp substrates (digoxin, dabigatran etexil, colchicine) and P-gp inhibitors (eg, cyclosporine, itraconazole, voriconazole, posaconazole and other azole antifungals, ritonavir, dronedarone, amiodarone, verapamil, clarithromycin, grapefruit juice), P-gp inducers (eg, rifampicin, St.
John's wort extract) should be cautious
.
If combined use is really necessary, blood drug concentration monitoring
is carried out if necessary.
Common adverse effects
of azvudine In a phase III clinical study of azvudine in the treatment of COVID-19, azvudine orally once daily (5 mg / time) for up to 14 days, similar to the adverse reactions of the control group, no statistical differences, mostly grade 1-2, common adverse reactions (incidence ≥ 1/100 to <1/10) include: ALT, AST, PLT, GGT mildly elevated, diarrhea
。 Adverse events included respiratory failure, the phase III study of azvudine was mainly included in patients with moderate infection, respiratory failure could occur in patients with moderate infection due to the high virulence of the virus strain, there was no significant difference between azvudine and control groups (1.
27% vs.
1.
27%), and azvudine itself did not increase the risk of
respiratory failure.
Azvudine adverse reactions countermeasures
Azvudine is safe and tolerated in a single administration of 1mg~5mg in HIV-infected patients, and the adverse reactions are mild, mainly manifested as fever, dizziness, nausea, diarrhea, etc.
And all of them are reported adverse reactions of similar anti-HIV drugs currently on the market, and can return to normal
with symptomatic treatment or no treatment.
<B156> Azvudine was well tolerated, had no significant effect on liver and kidney function in people with mild and moderate infection, and adverse events returned to normal quickly and were maintained until the end of treatment [13].
； For patients with diarrhea, it is necessary to distinguish whether it is caused by drugs or the virus itself, and symptomatic drugs can be taken; Patients with respiratory failure can be treated according to the relevant treatment principles, and if there is chest tightness and hypoxia, they need to go to the hospital for further observation
.
In general, azvudine, as an oral broad-spectrum RNA virus inhibitor, can effectively inhibit the replication of the new coronavirus and achieve the effect
of treating new coronary pneumonia (COVID-19).
It has fast onset, low dosage, significant efficacy in alleviating symptoms and shortening the course of the disease, and has good overall safety and tolerability, and has good clinical application prospects and accessibility in the treatment of new coronary pneumonia
.
In the face of every sudden attack of a variant, we will "save the risk"
home diagnosis and treatment services to protect everyone's health 👇
Resources:
[1] Chang Junbiao.
Research progress of oral small molecule drugs for the treatment of new coronary pneumonia[J].
China Science Foundation, 2022,
36(04): 630-634.
[2] CHANG Junbiao, BAO Xinhong, WANG Qiang et al.
2′-fluoro-4′-substituted-nucleoside analogue, preparation method and application: medium
China, ZL200710137548.
0, 2009-08-26.
[3] Chang J.
2'- Fluoro- 4'- Substituted Nucleosides, the Preparation and Use:
EP2177527B, 2013-12-18.
[4] Chang J.
2'- Fluoro - 4' - Substituted Nucleosides Analogues, Preparation Methods and Uses Thereof: US8835615B2, 2014-09-16.
[5] Chang JB.
4'- modified nucleosides for antiviral drug discovery: achievements and perspectives [J].
Accounts Chem Res, 2022, 55 (4): 565- 578.
[6] State Medical Products Administration.
The State Food and Drug Administration urgently approved the registration application of Henan Real Biotechnology Co.
, Ltd.
Azvudine tablets to add new coronary pneumonia treatment indications.
(2022-07-25)/[2022-08-08].
style="margin-left: 8px;margin-right: 8px;margin-bottom: 0px;line-height: normal;">[7] Medical Administration and Hospital Authority.
Notice on the inclusion of azvudine tablets in the diagnosis and treatment protocol for novel coronavirus pneumonia.
[EB/OL].
(2022-08-09)/[2022-12-02].
style="margin-left: 8px;margin-right: 8px;margin-bottom: 0px;line-height: normal;">e3ff4308b4446796c3f315601d436f.
shtml.
[8] Yu B, Chang J.
Azvudine (FNC): a promising clinical candidate for COVID-19treatment [J].
Signal Transduct Target Ther, 2020, 5(1): 236.
[9] Zhang JL, Li YH, Wang LL, et al.
Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients [J].
Signal Transduct Target Ther, 2021, 6: 414.
[10] Sun L, Peng YM, Yu WQ, et al.
Mechanistic insight into antiretroviral potency of 2'-deoxy-2'-β-fluoro-4'-azidocytidine (FNC) with a long-lasting effect on HIV-1 prevention [J].
J Med Chem, 2020, 63(15): 8554-8566.
[11] Liu Y, Wang Y, Peng Y, et al.
Effects of the antiretroviral drug 2'-deoxy-2'-β-fluoro-4'-azidocytidine (FNC) on P-gp, MRP2 and BCRP expressions and functions[J].
Pharmazie, 2018, 73(9): 503-507.
[12] Liu Y, Liu B, Zhang Y, et al.
Intestinal absorption mechanisms of 2'-deoxy-2'-β-fluoro-4'-azidocytidine, a cytidine analog for AIDS treatment, and its interaction with P-glycoprotein, multidrug resistance-associated protein 2 and breast cancer resistance protein [J].
Eur J Pharm Sci, 2017, 105: 150-158.
[13] Paula Cabral et al.
2022, PREPRINT (Version 1) available at Research Square.
