Pharmacokinetics and safety of silibinin in horses.
OBJECTIVE
To determine the oral bioavailability, single and multidose pharmacokinetics, and safety of silibinin, a milk thistle derivative, in healthy horses.


METHODS
9 healthy horses.


METHODS
Horses were initially administered silibinin IV and silibinin phospholipid orally in feed and via nasogastric tube. Five horses then consumed increasing orally administered doses of silibinin phospholipid during 4 nonconsecutive weeks (0 mg/kg, 6.5 mg/kg, 13 mg/kg, and 26 mg/kg of body weight, twice daily for 7 days each week).


RESULTS
Bioavailability of orally administered silibinin phospholipid was 0.6% PO in feed and 2.9% via nasogastric tube. During the multidose phase, silibinin had nonlinear pharmacokinetics. Despite this, silibinin did not accumulate when given twice daily for 7 days at the evaluated doses. Dose-limiting toxicosis was not observed.


CONCLUSIONS
Silibinin phospholipid was safe, although poorly bio-available, in horses. Further study is indicated in horses with hepatic disease.
Department of Clinical Sciences, College of Veterinary Medicine and Biological Sciences, Colorado State University, Fort Collins, CO, 80523.
Eileen S
ES
Hackett
Khursheed R
KR
Mama
David C
DC
Twedt
Daniel L
DL
Gustafson
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002853:Chromatography, Liquid; D004305:Dose-Response Relationship, Drug; D006736:Horses / Q000378:metabolism*; D007441:Intubation, Gastrointestinal / Q000662:veterinary; D013058:Mass Spectrometry; D020944:Silybum marianum / Q000737:chemistry*; D010936:Plant Extracts / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D010936:Plant Extracts; D012838:Silymarin; D000077385:Silybin