title: Chemical and biological stability of artemisinin in bovine rumen fluid and its kinetics in goats (Capra hircus).
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 degrees 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 (0.7 mug/mL) at 12 hours, and decreased to 0.18 mug/mL at 24 hours. At 24 hours, artemisinin concentration in feces was 2.4 mug/g, indicating its poor bioavailability in goats when provided orally and as capsules. These results suggest that the bioavailability of artemisinin to goats can improve 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.
authors.affiliation: USDA-ARS, Appalachian Farming Systems Research Center, 1224 Airport Rd, Beaver, WV25813, USA. jorge.Ferreira@ars.usda.gov
authors.forename: Jorge F S
authors.initials: JF
authors.lastname: Ferreira
authors.forename: Javier M
authors.initials: JM
authors.lastname: Gonzalez
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000032:analysis* / Q000493:pharmacokinetics*; D037621:Artemisinins / Q000032:analysis* / Q000493:pharmacokinetics*; D001826:Body Fluids / Q000737:chemistry*; D002417:Cattle; D004355:Drug Stability; D006041:Goats; D012417:Rumen
chemical_list: D000890:Anti-Infective Agents; D037621:Artemisinins; C031327:artemisinin