Hostname: page-component-cd9895bd7-hc48f Total loading time: 0 Render date: 2024-12-26T10:45:33.953Z Has data issue: false hasContentIssue false
  • English
  • Français

Clarithromycin, a cytochrome P450 inhibitor, can reverse mefloquine resistance in Plasmodium yoelii nigeriensis- infected Swiss mice

Published online by Cambridge University Press:  15 July 2011

RENU TRIPATHI ,
SWAROOP KUMAR PANDEY  and
AMBER RIZVI
RENU TRIPATHI*
Affiliation:
Division of Parasitology, Central Drug Research Institute (CSIR), Lucknow-226001, India
SWAROOP KUMAR PANDEY
Affiliation:
Division of Parasitology, Central Drug Research Institute (CSIR), Lucknow-226001, India
AMBER RIZVI
Affiliation:
Division of Parasitology, Central Drug Research Institute (CSIR), Lucknow-226001, India
*
*Corresponding author: Division of Parasitology, P.O.Box No. 173, Central Drug Research Institute (CSIR), Chattar Manzil Palace, Lucknow 226001, India. Tel: +91 522 2212411 18 Extn. 4461. Fax: +91 522 223405/223938. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

During the last 2 decades there have been numerous reports of the emergence of mefloquine resistance in Southeast Asia and nearly 50% resistance is reported in Thailand. A World Health Organization report (2001) considers mefloquine as an important component of ACT (artesunate+mefloquine) which is the first line of treatment for the control of uncomplicated/multi-drug resistant (MDR) Plasmodium falciparum malaria. In view of the emergence of resistance towards this drug, it is proposed to develop new drug combinations to prolong the protective life of this drug. Prior studies have suggested that mefloquine resistance can be overcome by a variety of agents such as ketoconazole, cyproheptadine, penfluridol, Icajine and NP30. The present investigation reports that clarithromycin (CLTR), a new macrolide, being a potent inhibitor of Cyt. P450 3A4, can exert significant resistance reversal action against mefloquine resistance of plasmodia. Experiments were carried out to find out the curative dose of CLTR against multi-drug resistant P. yoelii nigeriensis. Mefloquine (MFQ) and clarithromycin (CLTR) combinations have been used for the treatment of this MDR parasite. Different dose combinations of these two drugs were given to the infected mice on day 0 (prophylactic) and day 1 with established infection (therapeutic) to see the combined effect of these combinations against the MDR malaria infection. With a dose of 32 mg/kg MFQ and 225 mg/kg CLTR, 100% cure was observed, while in single drug groups, treated with MFQ or CLTR, the cure was zero and 40% respectively. Therapeutically, MFQ and CLTR combinations 32+300 mg/kg doses cleared the established parasitaemia on day 10. Single treatment with MFQ or CLTR showed considerable suppression of parasitaemia on day 14 but neither was curative. Follow-up of therapeutically treated mice showed enhanced anti-malarial action as reflected by their 100% clearance of parasitaemia. The present study reveals that CLTR is a useful antibiotic to be used as companion drug with mefloquine in order to overcome mefloquine resistance in plasmodia.

Keywords

Plasmodium yoelii nigeriensismalariaclarithromycinmefloquinedrug resistance
Type
Research Article
Information
Parasitology , Volume 138 , Issue 9 , August 2011 , pp. 1069 - 1076
Copyright
Copyright © Cambridge University Press 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Awasthi, A., Dutta, G. P., Bhakuni, V. and Tripathi, R. (2004). Resistance reversal action of ketoconazole against mefloquine resistance of Plasmodium yoelii nigeriensis (MDR). Experimental Parasitology 107, 115–119.Google Scholar
Baldwin, J., Gabriel, E. F., Friedman, P. A., Remy, D. C. (1991). Method of treating malaria with cyproheptadine derivatives. United States Patent 5021426.Google Scholar
Brophy, D. F., Isreal, D. S., Pastor, A., Gillotin, C., Chittick, G. E., Symonds, W. T., Lou, Y., Sadler, B. M. and Polk, R. E. (2000). Pharmacokinetic interaction between Amprenavir and clarithromycin in healthy male volunteers. Journal of Antimicrobial Agents and Chemotherapy 44, 978–984.CrossRefGoogle ScholarPubMed
Ciach, M., Zong, K., Kain, K. C. and Crandall, I. (2003). Reversal of mefloquine and quinine resistance in Plasmodium falciparum with NP30. Antimicrobial Agents and Chemotherapy 47, 2393–2396.Google Scholar
Dhawan, S., Awasthi, A., Tripathi, R., Puri, S. K. and Dutta, G. P. (2000). Reversal of chloroquine/mefloquine resistance of Plasmodium yoelii nigeriensis (MDR) by IFN-gamma and chloroquine resistance by Poly ICLC. Journal of Parasitic Diseases 24, 195–201.Google Scholar
Fontaine, F., Sousa, G.de., Burcham, P. C., Duchene, P. and Rahmani, R. (2000). Role of cytochrome P450 3A in the metabolism of mefloquine in human and animal hepatocytes. Life Sciences 66, 2193–2212.CrossRefGoogle Scholar
Frederich, M., Hayette, M. P., Tits, M., Mol, P. D. and Angenot, L. (2001). Reversal of chloroquine and mefloquine resistance in Plasmodium falciparum by the two monoindole alkaloids, Icajine and Isoretuline. Planta Medicine 67, 523–27.CrossRefGoogle ScholarPubMed
Gupta, S., Thapar, M. M., Wernsdorfer, W. H. and Bjorkman, A. (2002). In vitro interactions of artemisinin with atovaquone, quinine and mefloquine against plasmodium falciparum. Antimicrobial Agents and Chemotherapy 46, 1510–1515.CrossRefGoogle ScholarPubMed
Kyle, D. E., Milhous, W. K. and Odula, M. M. J. (1988). Reversal of mefloquine resistance in Plasmodium falciparum in vitro. 37th Annual Meeting of The American Society of Tropical Medicine and Hygiene, Washington, D.C. 4–8 December, 1988. p. 218.Google Scholar
Looareesuwan, S., Wilariatana, P., Viravan, C., Vanijanonta, S., Pitisutithum, P. and Kyle, D. E. (1997). Open randomized trial of oral artemether alone and a sequential combination with mefloquine for acute uncomplicated falciparum malaria. American Journal Tropical Medicine & Hygiene 56, 613–617.CrossRefGoogle Scholar
Malhotra-Kumar, S., Lammens, C., Coenen, S., Herck, K. V. and Goossens, H. (2007). Effect of azithromycin and clarithromycin therapy on pharyngeal carriage of macrolide-resistant streptococci in healthy volunteers: A randomised, double-blind, placebo-controlled study. Lancet 369, 482–490. doi:10.1016/S0140-6736(07)60235-9. PMID 17292768.Google Scholar
Mathis, A., Wild, E. C., Boettger, E. C., Kapel, C. M. O. and Deplazes, C. P. (2005). The mitochondrial ribosome as target for macrolide antibiotic clarithromycin in the helminth Echinococcus multiocularis. Antimicrobial Agents and Chemotherapy 49, 3251–3255.Google Scholar
Mathis, A., Wild, P., Deplazes, P. and Boettger, E. C. (2004). The mitochondrial ribosome of the protozoan Acanthamoeba castellanii is the target for macrolide antibiotics. Molecular and Biochemical and Parasitology 135, 225–229.CrossRefGoogle ScholarPubMed
Nosten, F., Kuile, F. T., Chongsaphajaisiddhi, T., White, N. J., Kuile, F. T., Luxemburger, C., Webster, H. K., Edstein, M., Phajpun, L., Thew, K. L. and White, N. J. (1991). MFQ resistant falciparum malaria on the Thailand- Burmese border. Lancet, 337, 1140–1143.CrossRefGoogle Scholar
Odoula, A. M., Omitowoju, G. O., Genera, L., Kyle, D. E., Milhouse, W. K., Sowunmi, A. and Salako, L. A. (1993). Reversal of mefloquine resistance with penfluoridol in isolates of Plasmodium falciparum from southwest Nigeria. Transaction of Royal Society of Tropical Medicine and Hygiene 87, 81–83.Google Scholar
Pai, M. P., Graci, D. M. and Amesden, G. W. (2000). Macrolide-drug interaction: An update. Annals of Pharmacotherapy 34, 495–513.CrossRefGoogle ScholarPubMed
Peters, W. and Robinson, B. L. (1991). The chemotherapy of rodent malaria. XLVI Reversal of mefloquine resistance in rodent Plasmodium. American Journal of Tropical Medicine and Parasitology 88, 5–10.CrossRefGoogle Scholar
Pinto, A. G., Wanq, Y. H., Chalasani, N., Skaar, T., Kolwankar, D., Gorski, J. C., Lianqpunsaqul, S., Hamman, M. A., Arefayene, M. and Hall, S. D. (2005). Inhibition of human intestinal wall metabolism by macrolide antibiotics: effect of clarithromycin on cytochrome P450 3A4/5 activity and expression. Clinical Pharmacological Therapy 77, 178–188.CrossRefGoogle ScholarPubMed
Price, R. N., Luxemburger, C., van Vugt, M., Simpson, J., Phaipun, L., Chongsuphajaisiddhi, T., Nosten, F. and White, N. J. (1998). Artesunate and mefloquine in the treatment of uncomplicated multidrug- resistant hyperparasitaemic falciparum malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene 92, 207–211.Google Scholar
Price, R. N., Nosten, F., Luxemburger, C., Kham, A. M., Brockman, A., Chongsuphajaisiddhi, T. and White, M. N. J. (1995). Artesunate versus artemether in combination with mefloquine for the treatment of multidrug resistant falciparum malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene 89, 523–527.Google Scholar
Ridtitid, W., Wongnawa, M. W., Mahatthanatrakul, W., Raungsri, N. and Sunbhanich, M. (2005). Ketoconazole increases plasma concentrations of antimalarial mefloquine in healthy human volunteers. Journal of Clinical Pharmacy and Therapeutics 30, 285–290.Google Scholar
Sinclair, D., Olliaro, P. and Garner, P. (2010). Guest Editorial: Artemisinin-based combination therapy for malaria, but which one? Clinical Evidence 8, 1–4.Google Scholar
Suzuki, A., Ilda, I., Hirota, M., Akimoto, M., Higuchi, S., Suwa, T., Tani, M., Ishizaki, T. and Chiba, K. (2003). Cyp isoforms invoved in the metabolism of CLTR in vitro: Comparison between the identification from disappearance rate and that from formation rate of metabolites. Drug Metabolism and Pharmacokinetics 18, 104–113.Google Scholar
Tripathi, R., Awasthi, A. and Dutta, G. P. (2005). Mefloquine resistance reversal action of ketoconazole- A cytochrome P450 inhibitor, against mefloquine resistant malaria. Parasitology 130, 475–479.Google Scholar
Westphal, J. F. (2000). Macrolide induced clinically relevant drug interactions with cytochrome P450 A (CYP) 3A4: an update focused on clarithromycin, azithromycin and dirithromycin. British Journal of Clinical Pharmacology 50, 285–295.Google Scholar
Wisedpanichkij, R., Chaijaroenkul, W., Sangsuwan, P., Tantisawat, J., Boonprasert, K. and Bangchang, K. N. (2009). In vitro antimalarial interactions between mefloquine and cytochrome P450 inhibitors. Acta Tropica 112, 12–15.Google Scholar
World Health Organization (2001). Antimalarial drug combination therapy: Report of WHO Technical Combination, Geneva, Switzerland. (WHO/CDS/RBM/2001·35)Google Scholar
World Health Organization (2004) The World Health Report 2004 – Changing Story. World Health Organization, Geneva, Switzerland.Google Scholar
World Health Organization (2006). Facts on ACTs (Artemisinin Based Combinations): An Update. World Health Organization, Geneva, Switzerland.Google Scholar
World Health Organization (2008). Malaria Report. World Health Organization, Geneva.Google Scholar
World Health Organization (2010 a). Malaria – Disease Burden in SEA Region. World Health Organization, Geneva, Switzerland.Google Scholar
World Health Organization (2010 b). Guidelines for the Treatment of Malaria. 2nd Edn. World Health Organization, Geneva, Switzerland.Google Scholar
Zhou, S. F. (2008). Drugs behave as substrates, inhibitors and inducers of human cytochrome P450 3A4. Current Drug Metabolism 9, 310–322.Google Scholar