title: Comparison of high-dose intermittent and low-dose continuous oral artemisinin in dogs with naturally occurring tumors.
abstract: To evaluate the clinical toxicity and activity of orally administered artemisinin in dogs with spontaneous tumors, 24 client-owned dogs were randomly divided into two groups and received either low-continuous dose (3 mg/kg q 24 hr) or high-dose intermittent (three doses of 45 mg/kg q 6 hr repeated q 1 wk) of artemisinin per os. Treatment was continued for 21 days. Dogs were evaluated weekly for clinical effect and at the end of the treatment for hematologic and biochemical adverse events. Whole blood concentrations of artemisinin and dihydroartemisinin were measured by liquid chromatography/tandem mass spectrometry after the first dose of artemisinin in three dogs in each group. Blood concentrations of artemisinin and dihydroartemisinin were <0.1 μM at all time points, and there was no difference in blood concentration between the two dosing groups. The most frequent adverse event was anorexia, which was observed in 11% of the low-dose group and 29% of the high-dose group. Oral artemisinin, both in low-dose continuous and high-dose intermittent, is well tolerated in dogs but results in low bioavailability. Parenteral administration should be considered for future studies.
authors.affiliation: Departments of Veterinary Clinical Sciences and Veterinary Biosciences (K.H., C.C., C.L., W.K.) and Division of Pharmaceutics, College of Pharmacy (M.P., J.D.), The Ohio State University, Columbus, OH.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hosoya
authors.forename: C Guillermo
authors.initials: CG
authors.lastname: Couto
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: London
authors.forename: William C
authors.initials: WC
authors.lastname: Kisseberth
authors.forename: Mitchell A
authors.initials: MA
authors.lastname: Phelps
authors.forename: James T
authors.initials: JT
authors.lastname: Dalton
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000662:veterinary; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity; D037621:Artemisinins / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity; D001682:Biological Availability; D002853:Chromatography, Liquid / Q000662:veterinary; D004283:Dog Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000662:veterinary; D007408:Intestinal Absorption; D053609:Lethargy / Q000139:chemically induced / Q000662:veterinary; D008297:Male; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000662:veterinary*
chemical_list: D000890:Anti-Infective Agents; D037621:Artemisinins; C031327:artemisinin