Effect of ritonavir/lopinavir on the efficacy of chloroquine and artemether/lumefantrine in mice
Keywords:
Artemether-lumefantrine, chloroquine, drug-drug interaction, lopinavir-ritonavir, Plasmodium bergheiAbstract
Background: Malaria co-infection with Human Immunodeficiency Virus (HIV) is common and its pharmacotherapy combines antiretroviral with antimalarial drugs, hence drug-drug interaction is inevitable. This study reports the effect of an antiretroviral drug, lopinavir/ritonavir (LPV/r) on the antimalarial activity of artemether/lumefantrine (AL) and chloroquine (CQ) in a mouse model of Plasmodium berghei.
Methodology: The standard procedures of prophylactic, suppressive and curative antiplasmodial assay models were adopted. The mice were divided into 6 groups of 5 mice each and 10 mg/kg, 6 mg/kg and 5 mg/kg body weight of CQ, LPV/r and AL were administered to groups 1, 2 and 3, respectively. The same dose of LPV/r and CQ was administered to group 4 concurrently, while group 5 received a similar dose of LPV/r and AL, concurrently. The mice in group 6 served as negative control.
Result: The study revealed that the co-administration of LPV/r with CQ and AL did not affect the suppressive antiplasmodial effect of CQ but boosted the parasite clearance of AL by 17.78 %. In the prophylactic test, the co-administration of LPV/r with CQ and AL also boosted the parasite clearance of CQ by 18.04 % and slightly boosted the parasite clearance of AL by 3.14 %. However, there was no significant effect of LPV/r on CQ and AL in the curative study.
Conclusion: Therefore, concurrent administration of LPV/r with AL and CQ affects mostly the suppressive and prophylactic effectiveness of AL and CQ, respectively.
References
Talakpo J, Skrlec I, Alebic T, Jukic M, Vcev A. Malaria: the Past and Present. Microorganisms 2019; 7(6): 179-184.
World Health Organization. Malaria in HIV Patients 2017. [updated: 2021 Nov 30; cited: 2022 Jun 5]. Available from: WHO | Malaria in HIV/AIDS patients. Accessed on 16/6/2022
Kublin JG, Patnaik P, Jere CS, Miller WC, Hoffman IF, Chimbiya N, Pendame R, Taylor TE, Molyneux ME Effect of Plasmodium falciparum malaria on concentration of HIV-1-RNA in the blood of adults in rural Malawi: a prospective cohort study. Lancet 2005;365:233–40.
Abu-Raddad LJ, Patnaik P, Kublin JG. Dual infection with HIV and malaria fuels the spread of both diseases in sub-Saharan Africa. Science. 2006;314:1603–6.
Byakika-Kibwika P, Lamorde M, Okaba-Kayom V, Mayanja-Kizza H, Katabira E, Hanpithakpong W, Pakker N, Dorlo TP, Tarning J, Lindegardh N, de Vries PJ, Back D, Khoo S, Merry C. Lopinavir/ritonavir significantly influences pharmacokinetic exposure of artemether/lumefantrine in HIV-infected Ugandan adults. The Journal of antimicrobial chemotherapy 2012; 67(5):1217 – 23.
Ashleigh R, Emily F, Shirley L. Ann SV. HIV-1 Impact on Malaria Transmission: A Complex and Relevant Global Health Concern. Frontiers in Cellular and Infection Microbiology 2921;11: 2235-2988. [updated: 2021 Feb 8; cited: 2022 Jun 5]. Available from: https://www.frontiersin.org/article/10.3389/fcimb.2021.656938.
Kwenti T. Malaria and HIV co-infection in sub-Saharan Africa: Prevalence, Impact and Treatment Strategies. Research and Reports in Tropical Medicine 2018; 9:123-136.
Hochman S, Kim K. The impact of HIV and Malaria Co-infection: what is known and suggested avenues for further study. Interdisciplinary Perspectives on Infectious Diseases 2009:8.
Kredo T, Mauff K, Workman L, Van der Walt JS, Wiesner L, Smith PJ, Maartens G, Cohen K, Barnes KI. The interaction between artemether-lumefantrine and lopinavir/ritonavir-based antiretroviral therapy in HIV-1 infected patients. BMC Infectious Diseases 2016; 16:30-43.
Parikh S, Kajubi R, Huang L, Ssebuliba J, Kiconco S, Gao Q, Li F, Were M, Kakuru A, Achan J, Mwebaza N, Aweeka FT. Antiretroviral Choice for HIV Impacts Antimalarial Exposure and Treatment Outcomes in Ugandan Children. Clin Infect Dis 2016;63(3): 414–422.
World Health Organization. Malaria 2021. [updated: 2021 Nov 6; cited: Mar 6]. Available from: https://www.who.int/news-room/fact-sheets/detail/malaria.
Global HIV and AIDs statistics. [updated: 2022 Mar 8; cited: 2022 Jun 6]. Available from: https://www.avert.org/printpdf/node/247
UNAIDS. AIDSinfo.unaids.org. Global data on HIV epidemiology and response. [updated: 2021 Jun 6; cited: 2022 Mar 6]. Available from: https://www.unaids.org/en/resources/fact-sheet
Bhatti A, Usman M, Kandi V. Current Scenario of HIV/AIDS, Treatment Options, and Major Challenges with Compliance to Antiretroviral Therapy. Cureus 2016; 8(3):1-12.
Chandwani A, Shuter J. Lopinavir/ritonavir in the treatment of HIV-1 infection: a review. Therapeutic and Clinical Risk Management 2008; 4(5):1023-1033.
Tse G, Korsik M, Todd H. The past, present and future of anti-malarial medicines.Malaria journal 2019;18:93-105.
Khoo S, Back D, Winstanley P. The potential for interactions between antimalarial and antiretroviral drugs. AIDS 2005;19:995–1005.
Weemhoff JL, von Moltke LL, Richert C, Hesse LM, Harmatz JS, Greenblatt DJ. Apparent mechanism-based inhibition of human CYP3A in-vitro by lopinavir. J Pharm Pharmacol. 2003 55(3):381-6.
Yeh RF, Gaver VE, Patterson KB, Rezk NL, Baxter-Meheux F, Blake MJ, Eron JJ Jr, Klein CE, Rublein JC, Kashuba AD. Lopinavir/ritonavir induces the hepatic activity of cytochrome P450 enzymes CYP2C9, CYP2C19, and CYP1A2 but inhibits the hepatic and intestinal activity of CYP3A as measured by a phenotyping drug cocktail in healthy volunteers. J Acquir Immune Defic Syndr 2006;42(1):52-60.
Agarwal S, Agarwal SK. Lopinavir-Ritonavir in SARS-CoV-2 Infection and Drug-Drug Interactions with Cardioactive Medications. Cardiovasc Drugs Ther 2021;35:427–440.
Barron AA, Kirsch RJ, Sandson NB, Nicholson WT, Marcucci C. Experimental COVID-19 Therapy Combination Lopinavir/Ritonavir Is Implicated in a Complicated Set of Drug-Drug Interactions. The Anesthesia Patient Safety Foundation. [updated: 2020 Jun 2; cited: 2022 Jun 5]. Available from: https://www.apsf.org/article/experimental-covid-19-therapy-combination-lopinavir-ritonavir-is-implicated-in-a-complicated-set-of-drug-drug-interactions/
Fellay J, Marzolini C, Decosterd L, Golay KP, Baumann P, Buclin T, Telenti A, Eap CB. Variations of CYP3A activity induced by antiretroviral treatment in HIV-1 infected patients. Eur J Clin Pharmacol. 2005;60(12):865-73.
German PI, Aweeka FT. Clinical pharmacology of artemisinin-based combination therapies. Clin Pharmacokinet. 2008;47:91–102.
Novartis Pharmaceuticals Corporation. Coartem (Artemether and Lumefantrine) Tablet: Human Prescription Drug Label. [updated: 2022 Mar 9; cited: 2022 Mar 4]. Available from: http://www.pharma.us.novartis.com/product/pi/pdf/ coartem.pdf.
Abdullahi S. T, Soyinka JO, Olagunju A, Bolarinwa RA, Olarewaju OJ, Bakare‐Odunola MT, Winterberg M, Tarning J, Owen A, Khoo S. CYP2B6*6 Genotype Specific Differences in Artemether‐Lumefantrine Disposition in Healthy Volunteers. J Clin Pharmacol 2020; 60(3): 351–360.
Kim K-A, Park J-Y, Lee J-S, Lim S. Cytochrome P450 2C8 and CYP3A4/5 are involved in chloroquine metabolism in human liver microsomes. Arch Pharm Res. 2003;26:631–637.
Smit C, Peeters MYM, van den Anker JN, Knibbe CAG. Chloroquine for SARS-CoV-2: Implications of Its Unique Pharmacokinetic and Safety Properties. Clin Pharmacokinet 2020;59:659–669.
Rendic SP, Guengerich FP. Metabolism and Interactions of Chloroquine and Hydroxychloroquine with Human Cytochrome P450 Enzymes and Drug Transporters. Current Drug Metabolism 2020;21(14):1127-1145.
Souza MAC, Reis NFA, Batista LS, César IC, Fernandes C, Pianetti GA. An easy and rapid spectrophotometric method for determination of chloroquine diphosphate in tablets. Current Pharmaceutical Analysis 2020;16:5-11.
Belew S, Suleman S, Duguma M, Teshome H, Wynendaele E, Duchateau L,Spiegeleer B. Development of a dissolution method for lumefantrine and artemether in immediate release fixed dose artemether/lumefantrine tablets. Malar J. 2020;19:139.
Killi GD, Maddinapudi RK, Dinakaran SK, Harani A. A novel validated UPLC method for quantitation of lopinavir and ritonavir in bulk drug and pharmaceutical formulation with its impurities. Brazilian Journal of Pharmaceutical Sciences 2020;50(2):302-307.
Okokon JE, Antia BS, Mohanakrishnan D, Sahal D. Antimalarial and antiplasmodial activity of husk extract and fractions of Zea mays. Pharm Biol 2017;55(1):1394-1400.
Nardos A, Makonnen E. In vivo antiplasmodial activity and toxicological assessment of hydroethanolic crude extract of Ajuga remota . Malar J 2017;16: 25.
Mengiste B, Makonnen E, Urga K. In vivo antimalarial activity of Dodonaea Angustifoliaseed extracts against Plasmodium berghei in mice model. Momona Ethiopian Journal of Science. 2012;4(1):47–63.
Asrade S, Mengesha Y, Moges G, Gelayee D. In vivo antiplasmodial activity evaluation of the leaves of Balanites rotundifolia (Van Tiegh.) Blatter (Balanitaceae) against Plasmodium berghei. Journal of Experimental pharmacology 2017;9:59-66.
Abiodun O, Gbimadee N, Gbotosho G. Lopinavir/ritonavir enhanced the antimalarial activity of amodiaquine and artesunate in a mouse model of Plasmodium berghei. Journal of Chemotherapy 2016;28(6): 482-486.
Abiodun O, Akinbo J, Ojurongbe O. The effect of lopinavir/ritonavir on the antimalarial activity of artemether or artemether/lumefantrine in a mouse model of Plasmodium berghei. Journal of chemotherapy 2015;27(1): 25-28.
Malvy D, Receveur MC, Ozon P, Djossou F, Le Metayer P, Touze JE, Longy-Boursier M, Le Bras M. Fatal cardiac incident after use of halofantrine. Journal of Travel Medicine 2000;7(4): 215-6.
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