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Amodiaquine–Ciprofloxacin: a potential combination therapy against drug resistant malaria

Published online by Cambridge University Press:  04 March 2015

Y. F. FALAJIKI
Affiliation:
Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, Nigeria Malaria Research Laboratories, Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria
O. AKINOLA
Affiliation:
Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, Nigeria Malaria Research Laboratories, Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria
O. O. ABIODUN
Affiliation:
Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, Nigeria Malaria Research Laboratories, Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria
C. T. HAPPI
Affiliation:
Malaria Research Laboratories, Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria Department of Biological Sciences, Redeemer University of Nigeria, Mowe, Ogun state, Nigeria
A. SOWUNMI
Affiliation:
Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, Nigeria Malaria Research Laboratories, Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria
G. O. GBOTOSHO*
Affiliation:
Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, Nigeria Malaria Research Laboratories, Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria
*
* Correspondence author. Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, Nigeria. E-mail: [email protected]

Summary

Emergence of malaria parasites resistant to artemisinin necessitates the need for development of new antimalarial therapies. Ciprofloxacin (CFX) a second generation quinolone antibiotic possesses some antimalarial activities. We investigated the in vivo antimalarial activities of CFX in combination with amodiaquine in mice infected with chloroquine-resistant Plasmodium berghei ANKA. Animals were treated orally with 80 or 160 mg kg−1 body weight of CFX alone given twice daily or in combination with amodiaquine (AQ) 10 mg kg−1 body weight. Parasitological activity and survival of the animals were assessed over 21 days. Peak parasitaemia in the untreated control group was 72·51%. Treatment with AQ alone resulted in clearance of parasitaemia by day 4 while treatment with CFX 80 and 160 mg kg−1 alone suppressed parasitaemia by 13·94–54·64% and 35·6–92·7%, respectively. However, the combination of CFX with AQ significantly enhanced response of infection in the animals to treatment (P < 0·05) resulting in complete resolution of parasitaemia throughout follow up period with CFX 160 mg kg−1, delayed recrudescence time with CFX 80 mg kg−1 and significant increase in survival rate of the animals. The results demonstrate beneficial interaction between AQ and CFX which may provide a clinically relevant antimalarial/antibiotic therapeutic option in the management of malaria.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2015 

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References

REFERENCES

Andrade, A. A., De Pilla Varotti, F., De Freitas, I. O., De Souza, M. V., Vasconcelos, T. R., Boechat, N. and Krettli, A. U. (2007). Enhanced activity of mefloquine and artesunic acid against Plasmodium falciparum in vitro and P. berghei in mice by combination with ciprofloxacin. European Journal of Pharmacology 558, 194198.CrossRefGoogle ScholarPubMed
Bustamante, C., Folarin, O. A., Gbotosho, G. O., Batista, C. N., Mesquita, E. A., Brindeiro, R. M., Tanuri, A., Struchiner, C. J., Sowunmi, A., Oduola, A., Wirth, D. F., Zalis, M. G. and Happi, C. T. (2012). In vitro reduced susceptibility to Artemether in P. falciparum and its association with polymorphism on transporter genes. Journal of Infectious Diseases 206, 324332.Google Scholar
Co, E. M. A., Johnson, S. M., Murthy, T., Talwar, M., Hickman, M. R. and Johnson, J. D. (2010). Recent methods in antimalarial susceptibility testing. Anti-Infective Agents in Medicinal Chemistry 9, 148160.Google Scholar
Dahl, E. L. and Rosenthal, P. J. (2007). Multiple antibiotics exert delayed effects against the Plasmodium falciparum apicoplast. Antimicrobial Agents and Chemotherapy 51, 34853490.Google Scholar
Da Silva, A. D., De Almeida, M. V., De Souza, M. V. and Couri, M. R. (2003). Biological activity and synthetic methodologies for the preparation of fluoroquinolones, a class of potent antibacterial agents. Current Medicinal Chemistry 19, 2139.CrossRefGoogle Scholar
Deloron, P., Lepers, J. P., Raharimalala, L., Dubois, B., Coulanges, P. and Pocidalo, J. (1991). Pefloxacin for falciparum malaria: only a modest success. Annals of Internal Medicine 114, 874875.Google Scholar
Dondorp, A. M., Nosten, F., Yi, P., Das, D., Phyo, A. P., Tarning, J., Lwin, K. M., Ariey, F., Hanpithakpong, W., Lee, S. J., Ringwald, P., Silamut, K., Imwong, M., Chotivanich, K., Lim, P., Herdman, T., An, S. S., Yeung, S., Singhasivanon, P., Day, N. P., Lindegardh, N., Socheat, D. and White, N. J. (2009). Artemisinin resistance in Plasmodium falciparum malaria. New England Journal of Medicine 361, 455467.Google Scholar
Gbotosho, G. O., Happi, C. T., Woranola, O., Abiodun, O. O., Sowunmi, A. and Oduola, A. M. (2012). Interaction between ciprofloxacin and chloroquine in mice infected with chloroquine resistant Plasmodium berghei . Parasitology Research 110, 895899.Google Scholar
Hamzah, J., Skinner-Adams, T. and Davis, T. M. (2000). In vitro antimalarial activity of trovafloxacin, a fourth-generation fluoroquinolone. Acta Tropical 74, 3942.Google Scholar
Ilo, C. E., Ezejiofor, N. A., Agbakoba, N., Brown, S. A., Maduagwuna, C. A., Agbasi, P. U. and Orisakwe, O. E. (2008). Effect of chloroquine on the urinary excretion of ciprofloxacin. American Journal of Therapeutics 15, 419422.Google Scholar
Ilo, E. C., Ilondu, N. A., Okwoli, N., Brown, S. A., Elo-Ilo, J. C., Agbasi, P. U. and Orisakwe, O. E. (2006). Effect of chloroquine on the bioavailability of ciprofloxacin in human. American Journal of Therapeutics 13, 432435.Google Scholar
Jambou, R., Legrand, E., Niang, M., Khim, N., Lim, P., Volney, B., Ekala, M. T., Bouchier, C., Esterre, P., Fandeur, T. and Mercereau-Puijalon, O. (2005). Resistance of Plasmodium falciparum field isolates to in-vitro artemether and point mutations of the SERCA-type PfATPase6. Lancet 366, 19601963.Google Scholar
Kazzim, O. J., Adegbolagun, O. M., Osho, O. and Anumudu, C. I. (2006). Additive effects of ciprofloxacin on the in-vitro activity of chloroquine against a clinical isolate of Plasmodium falciparum . Annals of Tropical Medicine and Parasitology 100, 579584.Google Scholar
Maciel, D., Fazio, M. A., Naaf_Pimenta, R. and Miranda, A. (2008). Anti Plasmodium activity of angiotensin II and related synthetic peptides. PLOS ONE 39, e3296.Google Scholar
Mahmoudi, N., Ciceron, L., Franetich, J. F., Farhati, K., Silvie, O., Eling, W., Sauerwein, R., Danis, M., Mazier, D. and Derouin, F. (2003). In vitro activities of 25 quinolones and fluoroquinolones against liver and blood stage Plasmodium spp. Antimicrobial Agents and Chemotherapy 47, 26362639.Google Scholar
McClean, K. L., Hitchman, D. and Shafran, S. D. (1992). Norfloxacin is inferior to chloroquine for falciparum malaria in northwestern Zambia: a comparative clinical trial. Journal of Infectious Diseases 165, 904907.Google Scholar
Noedl, H., Se, Y., Schaecher, K., Smith, B. L., Socheat, D. and Fukuda, M. M. (2008). Evidence of artemisinin-resistant malaria in western Cambodia. New England Journal of Medicine 359, 26192620.Google Scholar
Nzila, A., Ma, Z. and Chibale, K. (2011). Drug repositioning in the treatment of malaria and TB. Future Medicinal Chemistry 3, 14131426.Google Scholar
Pandey, S. K., Dwivedi, H., Singh, S., Siddiqui, W. A. and Tripathi, R. (2013). Antimalarial interaction of quinine and quinidine with clarithromycin. Parasitology 140, 406413.Google Scholar
Peters, W. (1965). Drug resistance in Plasmodium berghei I. Chloroquine resistance. Experimental Parasitology 17, 8089.Google Scholar
Phyo, A. P., Nkhoma, S., Stepniewska, K., Ashley, E. A., Nair, S., McGready, R., Moo, C. L., Al-Saai, S., Dondorp, A. M., Lwin, K. M., Singhasivanon, P., Day, N. P. J., White, N. J., Anderson, T. J. C. and Nosten, F. (2012). Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study. Lancet 379, 19601966.Google Scholar
Pradines, B., Rogier, C., Fusai, T., Mosnier, J., Daries, W., Barret, E. and Parzy, D. (2001). In vitro activities of antibiotics against Plasmodium falciparum are inhibited by iron. Antimicrobial Agents and Chemotherapy 45, 17461750.Google Scholar
Rogers, W. O., Sem, R., Tero, T., Chim, P., Lim, P., Muth, S., Socheat, D., Ariey, F. and Wongsrichanalai, C. (2009). Failure of artesunate-mefloquine combination therapy for uncomplicated Plasmodium falciparum malaria in southern Camodia. Malaria Journal 8, 10.Google Scholar
Salmon, D., Deloron, P., Gaudin, C., Malhotra, K., Lebras, J. and Pocidalo, J. J. (1990). Activities of perfloxacin and ciprofloxacin against experimental malaria in mice. Antimicrobial Agents and Chemotherapy 34, 23272330.Google Scholar
Sarma, P. S. (1989). Norfloxacin: a new drug in the treatment of falciparum malaria. Annals of Internal Medicine 111, 336337.Google Scholar
Sharma, P. C., Jain, A. and Jain, S. (2009). Fluoroquinolone antibacterials: a review on chemistry, microbiology and therapeutic prospects. Acta Poloniae Pharmaceutica 66, 587604.Google Scholar
Stromberg, A. and Bjorkman, A. (1992). Ciprofloxacin does not achieve radical cure of Plasmodium falciparum infection in Sierra Leone. Transactions of the Royal Society of Tropical Medicine and Hygiene 86, 373.Google Scholar
Tripathi, K. D., Sharma, A. K., Valecha, N. and Biswas, S. (1993). In vitro activity of fluoroquinolones against chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum . Indian Journal of Malariology 30, 6773.Google Scholar
Tripathi, R., Pandey, S. K. and Rizvi, A. (2011). Clarithromycin, a cytochrome P450 inhibitor, can reverse mefloquine resistance in Plasmodium yoelii nigeriensis-infected Swiss mice. Parasitology 138, 10691076.Google Scholar
Weisman, J. L., Liou, A. P., Shelat, A. A., Cohen, F. E., Guy, R. K., De Risi, J. L. (2006). Searching for new antimalarial therapeutics amongst known drugs. Chemical Biology and Drug Design 67, 409416.Google Scholar
Worldwide Antimalarial Resistance Network (2012). Malaria: Resistance to antimalarial drugs. /WWARN report.Google Scholar
World Health Organization (2010). Guidelines for Treatment of Malaria. World Health Organization, Geneva, Switzerland.Google Scholar
World Health Organization (2012). World Malaria Report 2012 Facts Sheet. World Health Organization, Geneva, Switzerland.Google Scholar
Yeo, A. E. T., Rieckmann, K. H. and Christopherson, R. I. (1998). Indirect inhibition by antibiotics of nucleotide and deoxynucleotide biosynthesis in Plasmodium falciparum . Southern Asian Journal of Tropical Medicine and Public Health 29, 2426.Google Scholar