Comparative Studies of the Pharmacokinetic Parameters of Dihydroartemisinin with its Disulphide Derivative.

Contenu principal de l'article

Emmanuel I. Etim
Imo E. Udoh
Gospel L. Ekanem.

Résumé

Malaria parasite has developed resistance to readily available and affordable drugs. Artemisinin and its derivatives are challenged by short systemic half life. The disulphide derivative of dihydroartemisinin was synthesized and confirmed of having antiplasmodial efficacy in vivo and is effective against gram negative bacteria and some fungi species in vitro. This work was aimed at assessing the pharmacokinetic parameters of the disulphide derivative of dihydroartemisinin in comparison with pure dihydroartemisinin. Sixty six rats of both sexes weighing between 180g to 220g were divided into twelve groups of five each. Therapeutic doses of dihydroartemisinin and the disulphide derivative were administered orally to each group. At interval of 1.0, 2.0, 4.0, 8.0, 12 and 24 hours, a group were sacrificed, and blood collected by cardiac puncture. The plasma obtained from the blood was spiked with benzene diazonium chloride and analyzed using UV spectrophotometer. The results obtained gave the pharmacokinetic parameters for the pure and disulphide derivative respectively as follows: AUC 9 mg.h/ml and 28.50 mg.h/ml, clearance 2.5 x 10-4 L/h/kg and 1.08 x 10-4 L/h/kg, volume of distribution 1.1 x 10-3 L/kg and 1.55 x 10-3 L/kg, elimination rate constant 0.24 h-1 and 0.070 h-1 and halflife 2.88 h and 9.9 h. The disulphide derivative with a halflife of 9.9h.,if proven clinically useful as a therapeutic agent could be used as a sustained release and dosed once daily for treatment of susceptible bacteria, fungi and malaria.

Téléchargements

Les données relatives au téléchargement ne sont pas encore disponibles.

Renseignements sur l'article

Comment citer
Etim, E. I. ., Udoh, I. E. ., & Ekanem., G. L. . (2020). Comparative Studies of the Pharmacokinetic Parameters of Dihydroartemisinin with its Disulphide Derivative. Nigerian Journal of Pharmaceutical and Applied Science Research, 7(2), 63–66. Consulté à l’adresse https://nijophasr.net/index.php/nijophasr/article/view/237
Rubrique
Articles
Bibliographies de l'auteur-e

Emmanuel I. Etim

Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, University of Uyo.

Imo E. Udoh

Department of Clinical Pharmacy and Biopharmacy, Faculty of Pharmacy, University of Uyo.

Gospel L. Ekanem.

Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, University of Uyo.

Références

Baird, J. K. (2013). Evidence and jimplications of mortality associated with acute Plasmodium vivax malaria. Clinical Microbiology Reviews. 26 (1): 36–57.

Bartoloni, A. and Zammarchi, L. (2012). Clinical aspects of uncomplicated and severe malaria. Mediterranean Journal of Hematology and Infectious Diseases. 4 (1): e2012026.

Coker, H.A.B.,Chukwuani, C.M., Ifudu, N. D. and Aina, B. A. , (2001).The malariascourge – concepts in disease management. Nigerian Journal of Pharmacy 32 : 402 – 406

Cumming J. N; Ploypradith P; Posner G. H. (1997). Antimalarial activity of artemisinin (qinghaosu) and related trioxanes: mechanism(s) of action. Adv. Pharmacol. Advances in Pharmacology. 37: 253–97.

Efferth, Thomas (2006). Molecular Pharmacology and Pharmacogenomics of Artemisinin and its Derivatives in Cancer Cells. Current Drug Targets. 7 (4): 407 – 21

Eseyin,A. O., Igboasoiyi, A. C., Igbo, C., Igboasoiyi, A., Ekarika, J. and Dooka, B. (2012). Effect of leaf extract of Veronia amygdalina on the pharmacokinetic of dihydroartemisinin in rat. Pharmacologia, 3 (12): 713 – 718.

Emmanuel E.,Aniefiok U., Ekarika J. and Etienne E. (2016).Development and validation of UV spectrophotometric method for determination of artesunate and dihydroartemisinin by coupling. The Phama Innovation Journal 5(8) :04 – 07.

Etim, E. I., Attih, E. E. and Owaba, (2017) Structural modification of dihydroartemisinin and antimicrobial assessment of the deoxy and disulphide derivatives. International Journal of Chemical Studies. 5(5): 2079 – 2083

Shargel, L. and Yu, ABC. Applied biopharmacokinetics and pharmacokinetics. Appleton Century Croft, New York, 1998 (3rd.ed), pp 68-101.

Nosten, F. and White N. J. (2007). Artemisinin-based combination treatment of falciparum malaria. American Journal of Tropical Medicine and Hygiene 77(6):181-192

Rang, HP., Dale, MM., Ritter, JM., Flower, RJ.,(2007).Rang and Dale’s Pharmacology,Elsevier Ltd., Churchill Livingstone. 6th. ed. pp 96; 113-130.

Rispin, A. Farrar, D, Margosches, E., Gupta, A.,Stitzel, K. (2002). Alternative methods for the median lethal dose LD50 test: The up-and-down procedure for acute toxicity. Institute for Laboratory Animal Research Journal 43(4): 233-243.

Walker , D. K. (2004).The use of pharmacokinetic and pharmacodynamic data in the assessment of drug safety in early drug development. British Journal of Clinical Pharmacology 58: 601-608.

Wallem, TE and Plowe, CV. (2001).Chloroquine resistant malaria. Journal of Infectious Disease, 182: 70 – 776.

White, N. J. (2014). Antimalarial drug resistance. The journal of clinical investigation 133 (8): 108-109.

World Health Organisation (WHO) (2015) World Malaria Report 2015, Geneva, Switzerland:--30-45