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Current Pharmaceutical Analysis

Editor-in-Chief

ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

Research Article

Development and Validation of In-vitro Release Study of Molnupiravir Capsules by RP-HPLC

Author(s): Shipra Singhal, Aman Sharma, Anirudh Malik, Meenakshi Dahiya, Gaurav Pratap Singh Jadaun, Vaishali M. Patil* and Shikha Kaushik

Volume 19, Issue 7, 2023

Published on: 28 August, 2023

Page: [577 - 585] Pages: 9

DOI: 10.2174/1573412919666230821102105

Price: $65

Abstract

Introduction: The coronavirus disease-2019 (COVID-19) outbreak all over the world has led researchers to strive to develop treatment and preventive measures to control its progression.

Methods: Molnupiravir, a prodrug of the synthetic nucleoside derivative N-4-hydroxycytidine was found to be a promising candidate against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

Results: It could significantly reduce the risk of hospitalization and mortality among patients with positive SARS-CoV-2 reports. In this study, an RP-HPLC method with UV detection was developed to determine its dissolution and release in the capsule dosage form. The developed method was validated as per International Council for Harmonization (ICH) guidelines.

Conclusion: The method was evaluated and validated for its applicability using various parameters. It was found to be a simple, rapid, selective, sensitive, accurate, precise, robust and rugged method.

Graphical Abstract

[1]
Joshi, S.; Parkar, J.; Ansari, A.; Vora, A.; Talwar, D.; Tiwaskar, M.; Patil, S.; Barkate, H. Role of favipiravir in the treatment of COVID-19. Int. J. Infect. Dis., 2021, 102, 501-508.
[http://dx.doi.org/10.1016/j.ijid.2020.10.069] [PMID: 33130203]
[2]
Schwartz, R.A.; Suskind, R.M. Azithromycin and COVID‐19: PROMPT early use at first signs of this infection in adults and children, an approach worthy of consideration. Dermatol. Ther., 2020, 33(4), e13785.
[http://dx.doi.org/10.1111/dth.13785] [PMID: 32510734]
[3]
Sultana, J.; Cutroneo, P.M.; Crisafulli, S.; Puglisi, G.; Caramori, G.; Trifirò, G. Azithromycin in COVID-19 patients: Pharmacological mechanism, clinical evidence and prescribing guidelines. Drug Saf., 2020, 43(8), 691-698.
[http://dx.doi.org/10.1007/s40264-020-00976-7] [PMID: 32696429]
[4]
Yip, A.J.W.; Low, Z.Y.; Chow, V.T.K.; Lal, S.K. Repurposing molnupiravir for COVID-19: The mechanisms of antiviral activity. Viruses, 2022, 14(6), 1345.
[http://dx.doi.org/10.3390/v14061345] [PMID: 35746815]
[5]
Verma, S.; Patil, V.M.; Gupta, M.K. Mutation informatics: SARS-CoV-2 receptor-binding domain of the spike protein. Drug Discov. Today, 2022, 27(10), 103312.
[http://dx.doi.org/10.1016/j.drudis.2022.06.012] [PMID: 35787481]
[6]
Echeverría-Esnal, D.; Martin-Ontiyuelo, C.; Navarrete-Rouco, M.E.; De-Antonio Cuscó, M.; Ferrández, O.; Horcajada, J.P.; Grau, S. Azithromycin in the treatment of COVID-19: A review. Expert Rev. Anti Infect. Ther., 2021, 19(2), 147-163.
[http://dx.doi.org/10.1080/14787210.2020.1813024] [PMID: 32853038]
[7]
Beigel, J.H.; Tomashek, K.M.; Dodd, L.E.; Mehta, A.K.; Zingman, B.S.; Kalil, A.C.; Hohmann, E.; Chu, H.Y.; Luetkemeyer, A.; Kline, S.; Lopez de Castilla, D.; Finberg, R.W.; Dierberg, K.; Tapson, V.; Hsieh, L.; Patterson, T.F.; Paredes, R.; Sweeney, D.A.; Short, W.R.; Touloumi, G.; Lye, D.C.; Ohmagari, N.; Oh, M.; Ruiz-Palacios, G.M.; Benfield, T.; Fätkenheuer, G.; Kortepeter, M.G.; Atmar, R.L.; Creech, C.B.; Lundgren, J.; Babiker, A.G.; Pett, S.; Neaton, J.D.; Burgess, T.H.; Bonnett, T.; Green, M.; Makowski, M.; Osinusi, A.; Nayak, S.; Lane, H.C. Remdesivir for the treatment of Covid-19-Final report. N. Engl. J. Med., 2020, 383(19), 1813-1826.
[http://dx.doi.org/10.1056/NEJMoa2007764] [PMID: 32445440]
[8]
Abd-Elsalam, S.; Noor, R.A.; Badawi, R.; Khalaf, M.; Esmail, E.S.; Soliman, S.; Abd El Ghafar, M.S.; Elbahnasawy, M.; Moustafa, E.F.; Hassany, S.M.; Medhat, M.A.; Ramadan, H.K.A.; Eldeen, M.A.S.; Alboraie, M.; Cordie, A.; Esmat, G. Clinical study evaluating the efficacy of ivermectin in COVID‐19 treatment: A randomized controlled study. J. Med. Virol., 2021, 93(10), 5833-5838.
[http://dx.doi.org/10.1002/jmv.27122] [PMID: 34076901]
[9]
Patil, V.M.; Verma, S.; Masand, N. Prospective mode of action of Ivermectin: SARS-CoV-2. Eur. J. Med. Chem. Reports, 2022, 4, 100018.
[http://dx.doi.org/10.1016/j.ejmcr.2021.100018] [PMID: 36593981]
[10]
Heidary, F.; Madani, S.; Gharebaghi, R.; Asadi-amoli, F. Acyclovir as a potential adjuvant therapy in COVID-19 treatment regimens. Ulum-i Daruyi, 2021, 27, S68-S77.
[http://dx.doi.org/10.34172/PS.2021.38]
[11]
Fischer, W.; Eron, J.; Holman, W.; Cohen, M.S.; Fang, L.; Szewczyk, L.J.; Sheahan, T.P.; Baric, R.; Mollan, K.R.; Wolfe, C.R.; Duke, E.R.; Azizad, M.M.; Borroto-Esoda, K.; Wohl, D.A.; Loftis, A.J.; Alabanza, P.; Lipansky, F.; Painter, W.P. Molnupiravir, an oral antiviral treatment for COVID-19. MedRxiv, 2021, 2021, 21258639.
[http://dx.doi.org/10.1101/2021.06.17.21258639]
[12]
Toots, M.; Yoon, J.J.; Cox, R.M.; Hart, M.; Sticher, Z.M.; Makhsous, N.; Plesker, R.; Barrena, A.H.; Reddy, P.G.; Mitchell, D.G.; Shean, R.C.; Bluemling, G.R.; Kolykhalov, A.A.; Greninger, A.L.; Natchus, M.G.; Painter, G.R.; Plemper, R.K. Characterization of orally efficacious influenza drug with high resistance barrier in ferrets and human airway epithelia. Sci. Transl. Med., 2019, 11(515), eaax5866.
[http://dx.doi.org/10.1126/scitranslmed.aax5866] [PMID: 31645453]
[13]
Painter, G.R.; Natchus, M.G.; Cohen, O.; Holman, W.; Painter, W.P. Developing a direct acting, orally available antiviral agent in a pandemic: The evolution of molnupiravir as a potential treatment for COVID-19. Curr. Opin. Virol., 2021, 50, 17-22.
[http://dx.doi.org/10.1016/j.coviro.2021.06.003] [PMID: 34271264]
[14]
News and communications. Available from: https://www.gov.uk/government/news/first-oral-antiviral-for-covid-19-lagevrio- (accessed on 02 January 2023)
[15]
Kumarasamy, N.; Saha, B.; Jindal, A.; Singh, V.B.; Reddy Podduturi, N.C.; Sinha, S.C. Phase III trial of Molnupiravir in adults with mild SARS-CoV-2 infection in India. Top. Antivir. Med., 2022, 30, 39.
[16]
Jayk Bernal, A.; Gomes da Silva, M.M.; Musungaie, D.B.; Kovalchuk, E.; Gonzalez, A.; Delos Reyes, V.; Martín-Quirós, A.; Caraco, Y.; Williams-Diaz, A.; Brown, M.L.; Du, J.; Pedley, A.; Assaid, C.; Strizki, J.; Grobler, J.A.; Shamsuddin, H.H.; Tipping, R.; Wan, H.; Paschke, A.; Butterton, J.R.; Johnson, M.G.; De Anda, C. Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients. N. Engl. J. Med., 2022, 386(6), 509-520.
[http://dx.doi.org/10.1056/NEJMoa2116044] [PMID: 34914868]
[17]
Fischer, W.A., II; Eron, J.J., Jr; Holman, W.; Cohen, M.S.; Fang, L.; Szewczyk, L.J.; Sheahan, T.P.; Baric, R.; Mollan, K.R.; Wolfe, C.R.; Duke, E.R.; Azizad, M.M.; Borroto-Esoda, K.; Wohl, D.A.; Coombs, R.W.; James Loftis, A.; Alabanza, P.; Lipansky, F.; Painter, W.P. A phase 2a clinical trial of molnupiravir in patients with COVID-19 shows accelerated SARS-CoV-2 RNA clearance and elimination of infectious virus. Sci. Transl. Med., 2022, 14(628), eabl7430.
[http://dx.doi.org/10.1126/scitranslmed.abl7430] [PMID: 34941423]
[18]
Rosenke, K.; Okumura, A.; Lewis, M.C.; Feldmann, F.; Meade-White, K.; Bohler, W.F.; Griffin, A.; Rosenke, R.; Shaia, C.; Jarvis, M.A.; Feldmann, H. Molnupiravir inhibits SARS-CoV-2 variants including Omicron in the hamster model. JCI Insight, 2022, 7(13), e160108.
[http://dx.doi.org/10.1172/jci.insight.160108] [PMID: 35579953]
[19]
Takashita, E.; Kinoshita, N.; Yamayoshi, S.; Sakai-Tagawa, Y.; Fujisaki, S.; Ito, M.; Iwatsuki-Horimoto, K.; Chiba, S.; Halfmann, P.; Nagai, H.; Saito, M.; Adachi, E.; Sullivan, D.; Pekosz, A.; Watanabe, S.; Maeda, K.; Imai, M.; Yotsuyanagi, H.; Mitsuya, H.; Ohmagari, N.; Takeda, M.; Hasegawa, H.; Kawaoka, Y. Efficacy of antibodies and antiviral drugs against Covid-19 omicron variant. N. Engl. J. Med., 2022, 386(10), 995-998.
[http://dx.doi.org/10.1056/NEJMc2119407] [PMID: 35081300]
[20]
Uraki, R.; Kiso, M.; Iida, S.; Imai, M.; Takashita, E.; Kuroda, M.; Halfmann, P.J.; Loeber, S.; Maemura, T.; Yamayoshi, S.; Fujisaki, S.; Wang, Z.; Ito, M.; Ujie, M.; Iwatsuki-Horimoto, K.; Furusawa, Y.; Wright, R.; Chong, Z.; Ozono, S.; Yasuhara, A.; Ueki, H.; Sakai-Tagawa, Y.; Li, R.; Liu, Y.; Larson, D.; Koga, M.; Tsutsumi, T.; Adachi, E.; Saito, M.; Yamamoto, S.; Hagihara, M.; Mitamura, K.; Sato, T.; Hojo, M.; Hattori, S.; Maeda, K.; Valdez, R.; Bennett-Baker, P.; Chu, Z.; Davis, D.; Kowalski-Dobson, T.; Eckard, A.; Gherasim, C.; Gremel, W.; Lindsey, K.; Manthei, D.; Meyers, A.; Moya, J.Z.; Rico, A.; Stoneman, E.; Blanc, V.; Sneeringer, S.; Warsinske, L.; Okuda, M.; Murakami, J.; Duong, C.; Godbole, S.; Douek, D.C.; Maeda, K.; Watanabe, S.; Gordon, A.; Ohmagari, N.; Yotsuyanagi, H.; Diamond, M.S.; Hasegawa, H.; Mitsuya, H.; Suzuki, T.; Kawaoka, Y. Characterization and antiviral susceptibility of SARS-CoV-2 Omicron BA.2. Nature, 2022, 607(7917), 119-127.
[http://dx.doi.org/10.1038/s41586-022-04856-1] [PMID: 35576972]
[21]
Tian, L.; Pang, Z.; Li, M.; Lou, F.; An, X.; Zhu, S.; Song, L.; Tong, Y.; Fan, H.; Fan, J. Molnupiravir and its antiviral activity against COVID-19. Front. Immunol., 2022, 13, 855496.
[http://dx.doi.org/10.3389/fimmu.2022.855496] [PMID: 35444647]
[22]
Painter, W.P.; Holman, W.; Bush, J.A.; Almazedi, F.; Malik, H.; Eraut, N.C.J.E.; Morin, M.J.; Szewczyk, L.J.; Painter, G.R. Human safety, tolerability, and pharmacokinetics of molnupiravir, a novel broad-spectrum oral antiviral agent with activity against SARS-CoV-2. Antimicrob. Agents Chemother., 2021, 65(5), e02428-e20.
[http://dx.doi.org/10.1128/AAC.02428-20] [PMID: 33649113]
[23]
Abdelnabi, R.; Maes, P.; de Jonghe, S.; Weynand, B.; Neyts, J. Combination of the parent analogue of remdesivir (GS-441524) and molnupiravir results in a markedly potent antiviral effect in SARS-CoV-2 infected Syrian hamsters. Front. Pharmacol., 2022, 13, 1072202.
[http://dx.doi.org/10.3389/fphar.2022.1072202] [PMID: 36605401]
[24]
Rabie, A.M.; Abdalla, M. Evaluation of a series of nucleoside analogs as effective anticoronaviral-2 drugs against the Omicron-B.1.1.529/BA.2 subvariant: A repurposing research study. Med. Chem. Res., 2022, 32(2), 1-16.
[PMID: 36593869]
[25]
Casalini, G.; Giacomelli, A.; Antinori, S. Liver tests abnormalities with licensed antiviral drugs for COVID-19: A narrative review. Expert Opin. Drug Saf., 2022, 21(12), 1483-1494.
[http://dx.doi.org/10.1080/14740338.2022.2160446] [PMID: 36597859]
[26]
Shannon, A.; Canard, B. Kill or corrupt: Mechanisms of action and drug-resistance of nucleotide analogues against SARS-CoV-2. Antiviral Res., 2023, 210, 105501.
[http://dx.doi.org/10.1016/j.antiviral.2022.105501] [PMID: 36567022]
[27]
Narkhede, R.R.; Cheke, R.S.; Shinde, S.D.; Kuchake, V.G.; Mahajan, N.M.; Patil, V.M. Understanding the dynamics of COVID-19 outbreak: Structure, diagnosis, prevention and treatment. Antiinfect. Agents, 2021, 19(4), e130621190363.
[http://dx.doi.org/10.2174/2211352519666210118094054]
[28]
Sinha, S.N.K.; Suram, V.K.; Chary, S.S.; Naik, S.; Singh, V.B.; Jain, M.K.; Suthar, C.P.; Borthakur, S.; Sawardekar, V.; Sk, N.; Reddy, N.; Talluri, L.; Thakur, P.; Reddy, M.; Panapakam, M.; Vattipalli, R. Efficacy and safety of molnupiravir in mild COVID-19 patients in India. Cureus, 2022, 14(11), e31508.
[http://dx.doi.org/10.7759/cureus.31508] [PMID: 36532902]
[29]
Johnson, D.M.; Brasel, T.; Massey, S.; Garron, T.; Grimes, M.; Smith, J.; Torres, M.; Wallace, S.; Villasante-Tezanos, A.; Beasley, D.W.; Comer, J.E. Evaluation of molnupiravir (EIDD-2801) efficacy against SARS-CoV-2 in the rhesus macaque model. Antiviral Res., 2023, 209, 105492.
[http://dx.doi.org/10.1016/j.antiviral.2022.105492] [PMID: 36535309]
[30]
Patil, V.M.; Singhal, S.; Masand, N. A systematic review on use of aminoquinolines for the therapeutic management of COVID-19: Efficacy, safety and clinical trials. Life Sci., 2020, 254, 117775.
[http://dx.doi.org/10.1016/j.lfs.2020.117775] [PMID: 32418894]
[31]
Suzuki, Y.; Shibata, Y.; Minemura, H.; Nikaido, T.; Tanino, Y.; Fukuhara, A.; Kanno, R.; Saito, H.; Suzuki, S.; Inokoshi, Y.; Sando, E.; Sakuma, H.; Kobayashi, T.; Kume, H.; Kamimoto, M.; Aoki, H.; Takama, A.; Iizuka, T.; Kamiyama, T.; Nakayama, M.; Saito, K.; Tanigawa, K.; Sato, M.; Waragai, Y.; Kambe, T.; Kanzaki, N.; Azuma, T.; Okamoto, H.; Sakamoto, K.; Nakamura, Y.; Ohtani, H.; Waragai, M.; Maeda, S.; Ishida, T.; Sugino, K.; Abe, W.; Tsukada, Y.; Lee, T.; Yamada, R.; Sato, R.; Onuma, T.; Tomita, H.; Saito, M.; Watanabe, N.; Rikimaru, M.; Kawamata, T.; Morimoto, J.; Togawa, R.; Sato, Y.; Saito, J.; Kanazawa, K.; Hamaguchi, S.; Iseki, K. Real-world clinical outcomes of treatment with molnupiravir for patients with mild-to-moderate coronavirus disease 2019 during the Omicron variant pandemic. Clin. Exp. Med., 2022, 1-9.
[http://dx.doi.org/10.1007/s10238-022-00949-3] [PMID: 36469171]
[32]
Kidd, M.R.; Kelly, P.M. PANORAMIC: Important insights into Molnupiravir use in COVID-19. Lancet, 2022, 401(10373), 250-251.
[http://dx.doi.org/10.1016/S0140-6736(22)02593-4] [PMID: 36566762]
[33]
Wise, J. Covid-19: Molnupiravir does not cut hospital admissions or deaths in vaccinated people at high risk, trial finds. BMJ, 2022, 379, o3055.
[http://dx.doi.org/10.1136/bmj.o3055] [PMID: 36564055]
[34]
Toots, M.; Yoon, J.J.; Hart, M.; Natchus, M.G.; Painter, G.R.; Plemper, R.K. Quantitative efficacy paradigms of the influenza clinical drug candidate EIDD-2801 in the ferret model. Transl. Res., 2020, 218, 16-28.
[http://dx.doi.org/10.1016/j.trsl.2019.12.002] [PMID: 31945316]
[35]
Thakur, S. Mayank; Sarkar, B.; Ansari, A.J.; Khandelwal, A.; Arya, A.; Poduri, R.; Joshi, G. Exploring the magic bullets to identify Achilles’ heel in SARS-CoV-2: Delving deeper into the sea of possible therapeutic options in Covid-19 disease: An update. Food Chem. Toxicol., 2021, 147, 111887.
[http://dx.doi.org/10.1016/j.fct.2020.111887] [PMID: 33253764]
[36]
Singla, S.; Goyal, S. Antiviral activity of molnupiravir against COVID-19: A schematic review of evidences. Bull. Natl. Res. Cent., 2022, 46(1), 62.
[http://dx.doi.org/10.1186/s42269-022-00753-9] [PMID: 35287311]
[37]
Padhi, A.K.; Shukla, R.; Saudagar, P.; Tripathi, T. High-throughput rational design of the remdesivir binding site in the RdRp of SARS-CoV-2: Implications for potential resistance. iScience, 2021, 24(1), 101992.
[http://dx.doi.org/10.1016/j.isci.2020.101992] [PMID: 33490902]
[38]
Annadi, A.M.; El Zahar, N.M.; El-Din, A.; Abdel-Sattar, N.; Mohamed, E.H.; Mahmoud, S.A.; Attia, M.S. Development and validation of molnupiravir assessment in bulk powder and pharmaceutical formulation by the RP-HPLC-UV method. RSC Advances, 2022, 12(53), 34512-34519.
[http://dx.doi.org/10.1039/D2RA05066H] [PMID: 36545624]
[39]
Gouda, A.S.; Marzouk, H.M.; Rezk, M.R.; Salem, A.M.; Morsi, M.I.; Nouman, E.G.; Abdallah, Y.M.; Hassan, A.Y.; Abdel-Megied, A.M. A validated LC-MS/MS method for determination of antiviral prodrug molnupiravir in human plasma and its application for a pharmacokinetic modeling study in healthy Egyptian volunteers. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2022, 1206, 123363.
[http://dx.doi.org/10.1016/j.jchromb.2022.123363] [PMID: 35810537]
[40]
Amara, A.; Penchala, S.D.; Else, L.; Hale, C.; FitzGerald, R.; Walker, L.; Lyons, R.; Fletcher, T.; Khoo, S. The development and validation of a novel LC-MS/MS method for the simultaneous quantification of Molnupiravir and its metabolite ß-d-N4-hydroxycytidine in human plasma and saliva. J. Pharm. Biomed. Anal., 2021, 206, 114356.
[http://dx.doi.org/10.1016/j.jpba.2021.114356] [PMID: 34509661]
[41]
Bindu, M.; Gandla, K.; Vemireddy, S.; Samuel, S.; Praharsha, Y. A validated stability indicating RP-HPLC method for the determination of Molnupiravir in pharmaceutical dosage form. World J. Adv. Res. Rev., 2022, 15(1), 580-590.
[http://dx.doi.org/10.30574/wjarr.2022.15.1.0720]
[42]
Reçber, T.; Timur, S.S. Erdoğan Kablan, S.; Yalçın, F.; Karabulut, T.C.; Neslihan Gürsoy, R.; Eroğlu, H.; Kır, S.; Nemutlu, E. A stability indicating RP-HPLC method for determination of the COVID-19 drug molnupiravir applied using nanoformulations in permeability studies. J. Pharm. Biomed. Anal., 2022, 214, 114693.
[http://dx.doi.org/10.1016/j.jpba.2022.114693] [PMID: 35276385]
[43]
Saraya, R.E.; Deeb, S.E.; Salman, B.I.; Ibrahim, A.E. Highly sensitive high‐performance thin‐layer chromatography method for the simultaneous determination of molnupiravir, favipiravir, and ritonavir in pure forms and pharmaceutical formulations. J. Sep. Sci., 2022, 45(14), 2582-2590.
[http://dx.doi.org/10.1002/jssc.202200178] [PMID: 35583051]
[44]
Camlik, G.; Beyazaslan, F.; Kara, E.; Ulker, D.; Albayrak, I.; Degim, I. A validated high-pressure liquid chromatography (HPLC) method for molnupiravir. Med. Res. Arch., 2022, 10(9), 1-9.
[http://dx.doi.org/10.18103/mra.v10i9.3127]
[45]
Sharaf, Y.A.; El Deeb, S.; Ibrahim, A.E.; Al-Harrasi, A.; Sayed, R.A. Two green micellar HPLC and mathematically assisted UV spectroscopic methods for the simultaneous determination of Molnupiravir and favipiravir as a novel combined COVID-19 antiviral regimen. Molecules, 2022, 27(7), 2330.
[http://dx.doi.org/10.3390/molecules27072330] [PMID: 35408729]
[46]
Reddy, K.T.K.; Haque, M.A. Develop and validate a highly sensitive method for the estimation of Molnupiravir in rat plasma by high performance liquid chromatography-tandem mass spectroscopy and its application to pharmacokinetic studies. J. Pharm. Negat. Results, 2022, 13(1), 28-34.
[47]
International Federation of Pharmaceutical Manufactures and Associations (IFPMA). Validation of analytical procedures: Text and methodology. Proceedings of the International Conference on Harmonization (ICH ’96), Methodology Q2 (R1), Geneva, Switzerland 1996.
[48]
Sutanto, S.T.; Sinto, R.; Pasaribu, A.; Shakinah, S. Molnupiravir and nirmatrelvir/ritonavir: The new available antiviral options for COVID-19. Acta Med. Indones., 2022, 54(4), 638-644.
[PMID: 36624705]
[49]
Santi Laurini, G.; Montanaro, N.; Motola, D. Safety profile of molnupiravir in the treatment of COVID-19: A descriptive study based on FAERS data. J. Clin. Med., 2022, 12(1), 34.
[http://dx.doi.org/10.3390/jcm12010034] [PMID: 36614834]
[50]
Najjar-Debbiny, R.; Gronich, N.; Weber, G.; Khoury, J.; Amar, M.; Stein, N.; Goldstein, L.H.; Saliba, W. Effectiveness of molnupiravir in high risk patients: A propensity score matched analysis. Clin. Infect. Dis., 2022, 76(3), 453-460.
[PMID: 36130189]
[51]
Donovan-Banfield, I.; Penrice-Randal, R.; Goldswain, H.; Rzeszutek, A.M.; Pilgrim, J.; Bullock, K.; Saunders, G.; Northey, J.; Dong, X.; Ryan, Y.; Reynolds, H.; Tetlow, M.; Walker, L.E.; FitzGerald, R.; Hale, C.; Lyon, R.; Woods, C.; Ahmad, S.; Hadjiyiannakis, D.; Periselneris, J.; Knox, E.; Middleton, C.; Lavelle-Langham, L.; Shaw, V.; Greenhalf, W.; Edwards, T.; Lalloo, D.G.; Edwards, C.J.; Darby, A.C.; Carroll, M.W.; Griffiths, G.; Khoo, S.H.; Hiscox, J.A.; Fletcher, T. Characterisation of SARS-CoV-2 genomic variation in response to molnupiravir treatment in the AGILE Phase IIa clinical trial. Nat. Commun., 2022, 13(1), 7284.
[http://dx.doi.org/10.1038/s41467-022-34839-9] [PMID: 36435798]
[52]
Nakamura, K.; Fujimoto, K.; Hasegawa, C.; Aoki, I.; Yoshitsugu, H.; Ugai, H.; Yatsuzuka, N.; Tanaka, Y.; Furihata, K.; Maas, B.M.; Wickremasingha, P.K.; Duncan, K.E.; Iwamoto, M.; Stoch, S.A.; Uemura, N. A phase I, randomized, placebo‐controlled study of molnupiravir in healthy Japanese to support special approval in Japan to treat COVID‐19. Clin. Transl. Sci., 2022, 15(11), 2697-2708.
[http://dx.doi.org/10.1111/cts.13395] [PMID: 36053806]

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