Serum concentration of Artemisinin after single and chronic oral dose administration in broiler chickens

Document Type : Research Articles

Authors

• jahangir Kaboutari ¹
• HossinAli Arab ²
• Saied Habibian Dehkordi ³
• Mahmood Rafiean ³
• Maysam Estaki ³

¹ Sُُُhahrekord University

² Tehran University

³ Shahrekord University

10.22067/veterinary.v8i1.50669

Abstract

Although preliminary studies have shown the anticoccidial effects of Artemisinin in broiler chickens, there are no proofs of its pharmacokinetics. The objective of this study was to determine the serum concentration of Artemisinin after single and multiple oral administration in broiler chickens. A total of 390 one-day-old healthy Ross 308 chickens were divided randomly into two groups. In the first group, single oral doses of 0, 1, 5, 25, 125, 250, 500 and 1000 mg/kg Artemisinin were given on day 44, and in the second group 0, 17, 34, 68 and 136 ppm of Artemisinin were given chronically in the diet over a 36-day period. An HPLC system with UV detector was used to determine serum level of Artemisinin. Data were presented as Mean ± SE and analyzed using the linear mixed model (p < 0.05). The results showed that in both groups the serum levels of Artemisinin were generally very low and there were no significant differences between multiple and single dose
administration groups or between different doses in each group (p < 0.05). The serum levels of Artemisinin in the chickens that had received single doses were in the range of 25.38 ± 0.15 to 42.27 ± 12.04 ng/ml and 24.68 ± 0.12 to 29.24 ± 1.72 ng/ml for those that had received chronic doses. It can be concluded that serum level of Artemisinin administered orally to the chickens as single or chronic doses is low which seems to be due to low oral absorption and metabolism induction and thus, can have high therapeutic index and good anticoccidial properties.

Keywords

• Artemisinin
• serum level
• Broiler Chickens
• HPLC

Main Subjects

• Pharmacology
• Poultry disease

---

References

Allen, PC. and Fetterer, R. (2002) Recent advances in biology and immunobiology of Eimeria species and in diagnosis and control of infection with these coccidian parasites of poultry. Clinical Microbiology Reviews 15, 58–65.

Allen, PC., Lydon, J., Danforth, HD. (1997) Effects of Artemisia annua on coccidiosis infection in chickens. Poultry Science 76, 1156-1163.

Arab, H.A., Kaboutari Katadj, J., Rahbari, S, Nabian, S., Soltan Mohammadi, A.R., Piali Kheirabadi, Kh. (2012) Comparison between anticoccidial effect of granulated extract of Artemisia seiberi and pure Artemisinin in affected broilers. Journal of Veterinary Research 67, 119-125.

Arab, H.A., Marhjanmehr, S.H. (2009) Toxicopathological effects of Artemisinin in broiler chicken following a single oral dose: an LD50 study. International Journal of Poultry Science 8, 808-812.

Arab, H.A, Rahbari, S., Rassouli A., et al.(2006) Determination of Artemisinin in Artemisia sieberi and anticoccidial effects of the plant extract in broiler chickens. Tropical Animal Health and Production 38, 497-503.

Ashton, M., Gordi, T., Hai, T.N., et al. (1998a) Artemisinin phamacokinetics in healthy adults after 250, 500 and 1000 mg single oral doses. Biopharmaceutical & Drug Disposition 19, 245-250.

Ashton, M., Hia, T.N., Sy, N.D., et al. (1998b)Artemisinin pharmacokinetics is time dependent during repeated oral administration in healthy male adults. Drug Metabolism and Disposition 26, 25-27.

Ashton, M., Sy, N.D., Huong, N.V., et al. (1998c)Artemisinin kinetics and dynamics during oral and rectal treatment of uncomplicated malaria. Clinical Pharmacology & Therapeutics 63, 482-493.

Asimus, S. and Gordi T. (2006) Retrospective analysis of Artemisinin pharmacokinetics: application of a semi physiological autoindution model. British Journal of Pharmacology 63, 758-762.

Asimus, S., Elsherbiny, D., Hai, T.N., et al. (2007) Artemisinin antimalarials moderately affect cytochrome P450 enzyme activity in healthy subjects. Fundamental & Clinical Pharmacology 21, 307-316.

Brisibe, E.A., Umoren, U.E., Owai, P.U., et al. (2008) Dietary inclusion of dried Artemisia annua leaves for management of coccidiosis and growth enhancement in chickens. African Journal of Biotechnology 27, 4083-4092.

China cooperative research group. (1982) Studies on the toxicity of quighaosu and its derivatives. Journal of Traditional Chinese Medicine 2, 31-38.

Dalloul, R.A. and Lillehoj, H.S. (2006) Poultry coccidiosis: recent advances in control measures and vaccine development. Expert Review of Vaccines 5, 143-163.

Golenser, J., Waknine, J.H., Krugliak, M., at al. (2006) Current perspective on the mechanism of action of Artemisinin. International Journal of Parasitology 36, 1427-1441.

Gordi, T., Huong, D.X., Hai, T.N., et al. (2002) Artemisinin pharmacokinetics and efficacy in uncomplicated malaria patients treated with two different dosage regimens. Antimicrobial Agents and Chemotherapy 46, 1026-1031.

Gordi, T., Xie, R., Huong, N.V., et al. (2005a) A semiphysiological pharmacokinetic model for Artemisinin in healthy subjects incorporating autoinduction of metabolism and saturable first-pass hepatic extraction. British Journalof Clinical Pharmacology 59, 189-198.

Gordi, T., Xie, R., Jusko, W.J. (2005b) Semi-mechanistic pharmacokinetic/pharmacodynamic modeling of the antimalarial effects of Artemisinin. British Journal of Clinical Pharmacology 60, 594-604.

Gregory,R.T. (2002) A bird’s eye views of the C-valve enigma genome: Genome Size, cell size and metabolic rate in the class. Evolution 56, 121-130.

Gu, Y. and Li, Q. (2008) Comparison of HPLC with electrochemical detection and LC-MS/MS for the separation and validation of Artemisinin and dihydroArtemisinin in animal and human plasma. Journal of Chromatography B867, 213-218.

Guidelines for industry, bioanalytical method validation. (2001) IOP Publishing FDA Web. http://fda.gov/downloads/drugs/ Guideline compliance regulatory information/Guideline/ ucm 070107. 1-25

Huang, L., Jayewardene, A.L., Li, X., et al. (2009) Development and validation of a high performance liquid chromatography/tandem mass spectrometry method for the determination of artemether and its active metabolite dihydro Artemisinin in human plasma. Journal of Pharmaceuticaland Biomedicine Analysis 5, 959-965.

Kaboutari, J., Arab, H.A., Ebrahimi, K., Rahbari, S. (2014) Prophylactic and therapeutic effects of a novel granulated formulation of Artemisia extract on broiler coccidiosis. Tropical Animal Health and Production 46, 43-48.

Liersch, R., Soicke, H., Stehlr, C., et al. (1996) Formulation of Artemisinin in Artemisia annua during one vegetation period. Planta Medicine 52, 387-390.

Meshnick, S.R., Tsang, T.W., Lin, T, W., et al. (1998) Activated

oxygen mediates the antimalarial activity of quinghaosu. Progress in Clinical and Biological Research 313, 95-104.

Naidoo, V., McGaw, L. J., Bishop, S.R.P., et al. (2008) The value of plant with antioxidant activity in attenuating coccidiosis in broiler chickens. Veterinary Parasitology 153, 241-219.

Oh, H.G., Youn, H.J., Noh, J.W., et al.(1995a) Anticocccidial effects of an extract of Artemisia annua on the Eimeria tenella. Korean Journal of Veterinary Research 35,115-121.

Oh, H.G., Youn, H.J., Noh, J.W., et al. (1995b) Anticoccodial effects of Artemisinin on the Eimeria tenella.Korean Journal of Veterinary Research 35, 123-130.

Ollario, P.L. and Taylor, W.R. (2004) Developing Artemisinin based drug combination for treatment of drug resistant falciparum malaria. Journal of Postgraduate Medicine 50, 40-44.

Pirali Kheirabadi, K., Kaboutari Kkatadj, J., Bahadoran, S., et al. (2014) Comparison of anticoccidial effects of granulated extract of Artemisia sieberi with monensin in experimental coccidiosis in broiler chickens. Experimental Parasitology 141, 129-133.

Rawa-Adkonis, M., Wolska, L., Namiesnik, J. (2003) Modern techniques of extraction of organic analytes from environmental matrices. Critical Reviews of Analytical Chemistry 33, 199-248.

Shah, V.P., Midha, K.K., Dighe, S., et al. (2001) Analytic method validation bioavailability bioequivalence and pharmacokinetic studies. European Journal of Drug Metabolism and Pharmacokinetics 16, 249-255.

Shahbazfar, A.A., Mardjanmehr, S.H., Arab H.A., et al. (2011) Effects of Artemisinin in broiler chickens following chronic oral administration. Tropical Animal Health and Production 43, 843-849.

Simonsson, U.S., Jansson, B., Hai, T.N., et al. (2003)Artemisinin autoindution is caused by involvement of cytochrome P4502B6 but not 2C9. Clinical Pharmacology and Therapeutics 74, 32-43.

Svensson, U.S., Ashton, M., Hai, T.N., et al. (1998) Artemisinin induces omeprazole metabolism in human beings. Clinical Pharmacology and Therapeutics 64, 160-167.

Titulaer, H.A.C., Zuidema, J., Lugt, C.B. (1991) Formulation and pharmacokinetics of Artemisinin and its derivatives. International Journal of Pharmaceutics 69, 83-92.

Weinberg, E.D., and Moon, J. (2009) Malaria and iron: history and review. Drug Metabolism Reviews 41, 644-662.

Willcox, M., Falquet, J., Ferreira, J.F., et al. (2007)Artemisia annua as a herbal tea for malaria. African Journal of Traditional Complementary Alternative Medicine 4, 121-123.

Wong, J.W., and Yuen, K.H. (2001) Improved oral bioavailability of Artemisinin through inclusion complexation with β and γ –cyclodextrins. International Journal of Pharmaceutics 227, 177-185.

Woodrow, C.J., Hayns RK, Krishna S. (2005) Artemisinins. Postgraduate Medicine Journal 81, 71-78.

Xing J, Yan, H., Zhang, S. (2006) A high performance liquid chromatography/ tandem mass spectrometry method for the determination of Artemisinin in rat plasma. Rapid Communication Mass Spectrometry 20, 1463-1468.

Zhang, Z., and Zeng, M. (2005) Research advances of drug resistance in chickens’ coccidiosis. Chinese Journal of Veterinary Parasitology Research 13, 29-36.

Zhu, D. (1987) Recent advances on the active components in Chinese medicines. Abstract of Chinese Medicine, 251-266.