CHEMICAL AND BIOLOGICAL STABILITY OF ARTEMISININ IN COW RUMEN FLUID AND ITS KINETICS IN GOATS (CAPRA HIRCUS)

Authors: Ferreira, Jorge; Gonzalez, Javier

Submitted to: Brazilian Journal of Veterinary Parasitology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/1/2008
Publication Date: 12/31/2008
Citation: Ferreira, J.F., Gonzalez, J.M. 2008. CHEMICAL AND BIOLOGICAL STABILITY OF ARTEMISININ IN COW RUMEN FLUID AND ITS KINETICS IN GOATS (CAPRA HIRCUS). Brazilian Journal of Veterinary Parasitology. 17(1):103-109.

Interpretive Summary: The barber pole worm is a parasite that lives in the stomach of small ruminants. This organism is resistant to most available drugs used to control parasites of the digestive system in ruminants. Consequently, significant economic loss occurs due to stress, weight loss, and death of host animals. Anti-parasitic natural compounds extracted from the sweet wormwood plant are used to treat drug-resistant malaria. While effective against the malaria parasite, the possibility of using these compounds in veterinary medicine is just now being considered. We evaluated different formulations of the main active compound produced by sweet wormwood in a series of highly controlled laboratory experiments. We found that the compound was stable in a range of conditions typical of the ruminant digestive system, and that the active compound can reach the goat’s blood becoming a potential parasite killer. Our findings show promise for using sweet wormwood as a natural source of biological-control agents against parasites in small ruminants.

Technical Abstract: There is a pressing need to develop alternative, natural anthelmintics to control widespread drug-resistant gastrointestinal nematodes in ruminants, such as Haemonchus contortus. Artemisinin and its semi-synthetic derivatives are widely used against drug-resistant Plasmodium falciparum, but their role in veterinary medicine is only emerging. Artemisinin may be useful in controlling gastrointestinal parasites including Haemonchus. However, no ruminant studies involving artemisinin have been reported. The stability of artemisinin in capsules, crystals, or stock solutions in ethanol and dimethyl sulfoxide was evaluated in bovine rumen culture medium incubated for 24 hours at 39 deg C. A second study established artemisinin kinetics in goats after oral administration of artemisinin capsules at 23 mg/kg of body weight. Artemisinin recovered from rumen culture ranged from 67 to 92% at pH 6.8 and was 95% at pH 3.0. The kinetics data showed that artemisinin was metabolized to dihydroartemisinin by goats, while unabsorbed artemisinin was eliminated in feces. Dihydroartemisinin peaked in the blood (0.7ug/mL) at 12 hours, and decreased to 0.18 ug/mL at 24 hours. At 24 hours, artemisinin concentration in feces was 2.4 ug/g, indicating its poor bioavailability in goats when provided orally and as capsules. These results suggest that the bioavailability of artemisinin to goats could be improved by dissolving capsules in ethanol or dimethyl sulfoxide, by using more stable and bioavailable artemisinin-derived drugs, and by using routes of delivery other than oral.