Hosoya Kenji, Couto C Guillermo, London Cheryl A, Kisseberth William C, Phelps Mitchell A, Dalton James T
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.
J Am Anim Hosp Assoc. 2014 Nov-Dec;50(6):390-5. doi: 10.5326/JAAHA-MS-6145. Epub 2014 Sep 23.
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.
为评估口服青蒿素对患有自发性肿瘤犬的临床毒性和活性，将24只客户拥有的犬随机分为两组，分别接受低剂量持续给药（3毫克/千克，每24小时一次）或高剂量间歇给药（三剂，45毫克/千克，每6小时一次，每周重复一次）的青蒿素口服治疗。治疗持续21天。每周对犬进行临床效果评估，并在治疗结束时评估血液学和生化方面的不良事件。每组三只犬在首次服用青蒿素后，通过液相色谱/串联质谱法测定青蒿素和双氢青蒿素的全血浓度。所有时间点的青蒿素和双氢青蒿素血药浓度均<0.1微摩尔，两个给药组的血药浓度无差异。最常见的不良事件是厌食，低剂量组有11%的犬出现，高剂量组有29%的犬出现。低剂量持续给药和高剂量间歇给药的口服青蒿素在犬中耐受性良好，但生物利用度较低。未来研究应考虑采用胃肠外给药途径。
