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Is halofantrine ototoxic? Experimental study on guinea pig cochlea model

Published online by Cambridge University Press:  11 June 2010

N M Iskander ,
T F Youssef ,
M R Ahmed  and
A A K Mohamed
N M Iskander
Affiliation:
Department of Otolaryngology, Faculty of Medicine and the Suez Canal University, Ismailia, Egypt
T F Youssef
Affiliation:
Department of Otolaryngology, Faculty of Medicine and the Suez Canal University, Ismailia, Egypt
M R Ahmed*
Affiliation:
Department of Otolaryngology, Faculty of Medicine and the Suez Canal University, Ismailia, Egypt
A A K Mohamed
Affiliation:
Department of Otolaryngology, Faculty of Medicine and the Suez Canal University, Ismailia, Egypt
*
Address for correspondence: Dr M R Ahmed, Faculty of Medicine, Suez Canal University, Ismailia, Egypt. Fax: +20 66 3415603 E-mail: [email protected]
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Abstract

Introduction:

Halofantrine is a newly developed antimalarial drug used for the treatment of Plasmodium falciparum malaria. The introduction of this drug has been delayed because of its possible side effects, and due to insufficient studies on adverse reactions in humans. There have been no studies investigating its effect on hearing.

Methods:

Thirty guinea pigs were divided into three groups: a control group, a halofantrine therapeutic dose group and a halofantrine double therapeutic dose group. One cochlea specimen from each animal was stained with haematoxylin and eosin and the other with toluidine blue.

Results:

No changes were detected in the control group. The halofantrine therapeutic dose group showed loss and distortion of inner hair cells and inner phalangeal cells, and loss of spiral ganglia cells. In the halofantrine double therapeutic dose group, the inner and outer hair cells were distorted and there was loss of spiral ganglia cells.

Conclusion:

Halofantrine has mild to moderate pathological effects on cochlea histology, and can be considered an ototoxic drug.

Keywords

HalofantrineDrug ToxicityOtotoxicityCochleaGuinea Pig
Type
Main Articles
Information
The Journal of Laryngology & Otology , Volume 124 , Issue 10 , October 2010 , pp. 1061 - 1066
Copyright
Copyright © JLO (1984) Limited 2010

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References

1Batey, AJ, Lightbown, ID, Lambert, JP, Edwards, G, Coker, SJ. Comparison of the acute cardiotoxicity of the antimalarial drug halofantrine in vitro and in vivo in anaesthetized guinea-pigs. Br J Pharmacol 1997;122:563–9CrossRefGoogle ScholarPubMed
2Baune, B, Flinois, J, Furlan, VFG, Taburet, A, Becquemont, L, Farlnotti, R. Halofantrine metabolism in microsomes in man: major role of CYP 3A4 and CYP 3A5. J Pharm Pharmacol 1999;51:419–26CrossRefGoogle ScholarPubMed
3Ter Kuile, FO, Dolan, G, Nosten, F, Edstein, MD, Luxemburger, C, Phaipun, L. Halofantrine versus mefloquine in treatment of multidrug-resistant falciparum malaria. Lancet 1993;341:1044–9CrossRefGoogle ScholarPubMed
4White, NJ. Delaying antimalarial drug resistance with combination chemotherapy. Parassitologia 1999;41:301–8Google ScholarPubMed
5Connell, MB. History of treatment and prophylaxis of malaria. In: Emilio, Pampana. RPH Laboratory Medicine, 5th edn.New York, NY: Oxford University Press, 1998;643–51Google Scholar
6Nosten, F, McGready, R, d'Aleessandro, U, Nonell, A, Verhoeff, F, Menenez, C et al. Antimalarial drugs in pregnancy: a review. Curr Drug Saf 2006;1:1–15CrossRefGoogle ScholarPubMed
7Nyunt, MM, Plowe, CV. Pharmacologic advances in the global control and treatment of malaria: combination therapy and resistance. Clin Pharmacol Ther 2007;82:601–5CrossRefGoogle ScholarPubMed
8Jung, TTK, Rhee, CK. Ototoxicity of salicylate, nonsteroidal anti-inflammatory drugs and quinine. Otol Clin 1993;26:791–810Google ScholarPubMed
9Winstanley, P, Ward, S. Malaria chemotherapy. Adv Parasitol 2006;61:47–76CrossRefGoogle ScholarPubMed
10Miller, JJ. Handbook of Ototoxicity. Boca Raton, Florida: CRC Press, 1985Google Scholar
11Makanga, M, Premji, Z, Falade, C, Karbwang, J, Mueller, EA, Andriano, K. Efficacy and safety of the six dose regimen of artemether lumefantrine in pediatrics with uncomplicated Plasmodium falciparum malaria: a pooled analysis of individual patient data. Am J Trop Med Hyg 2006;74:991–8CrossRefGoogle Scholar
12Yung, MW, Wright, A. An improved morphological technique for the study of cochleotoxicity in guinea pigs. J Laryngol Otol 1998;100:1235–44CrossRefGoogle Scholar
13Steven, A. The haematoxylins: In: Bancroft, JD, Stevens, A, eds. Theory and Practice of Histological Techniques, 3rd edn.Edinburgh: Churchill Livingstone, 1990;107–11Google Scholar
14Bancroft, JD, Cook, HC. Central and peripheral nervous system. In: Sterling, RW, Turner, DP. Manual of Histological Techniques and their Diagnostic Application. Edinburgh: Churchill Livingstone, 1994;343–72Google Scholar
15Touze, JF, Fourcade, L, Peyrone, F, Heno, P, Deharo, JC. Is halofantrine still advisable in malaria attack? Ann Trop Med Parasitol 1997;91:867–73CrossRefGoogle Scholar
16Horton, J. Halofantrine in the treatment of malaria. Drug Saf 1995;13:271–2Google ScholarPubMed
17Diadia, BC, Gbigbi, PS, Dapper, DV. Preliminary study on the effect of halofantrine on the testes of mature Wister rats. Journal of Applied Sciences and Environmental Management 2002;6:45–8Google Scholar
18Obi, E, Orisakwe, OE, Asomugha, LA, Udemezue, OO, Orish, VN. The hepatotoxic effect of halofantrine in guinea pigs. Indian J Pharmacol 2004;36:303–5Google Scholar
19Berninger, E, Gustafsson, LL. Changes in 2f1-f2 acoustic distortion products in humans during quinine-induced cochlear dysfunction. Acta Otolaryngol 2000;120:600–6CrossRefGoogle ScholarPubMed
20Bassi, PU, Buratai, BL, Kuchali, W. Effect of halofantrine administration on some liver and heart enzymes in healthy human volunteers. Afr J Biomed Res 2006;9:31–5Google Scholar