By Jill Griffiths and Karin Zitterl-Eglseer, AoUnivProf, MagPharm, DrRerNat
The increasing popularity of alternative treatments has led to a rise in the use of devil’s claw extracts to treat chronic pain and inflammation in horses. But with little known about how the equine body responds to the plant’s active ingredients, it has been difficult to determine appropriate doses. Researchers recently evaluated horses’ response to harpagoside, the active ingredient in devil’s claw (Harpagophytum procumbens).
Karin Zitterl-Eglseer, AoUnivProf, MagPharm, DrRerNat, of the University of Veterinary Medicine, in Vienna, Austria, said devil’s claw has been used to treat inflammatory and degenerative disorders in horses for many years but without the substantive pharmacokinetic data. Pharmacokinetics is the study of drug absorption, distribution, and excretion.
“This sort of data is important in working out appropriate doses and treatment regimes,” Zitterl-Eglseer said.
“Devil’s claw has gained an international reputation as a potent anti-inflammatory and analgesic agent,” she said. “It is proposed as an alternative to NSAIDs (non-steroidal anti-inflammatory drugs) in cases of chronic pain where the horse requires ongoing, daily pharmaceutical support. In these cases, the use of NSAIDs such as phenylbutazone (Bute) is limited by their possible long-term side-effects, such as gastric and intestinal ulcers.”
In their study Zitterl-Eglseer and colleagues used six clinically healthy Warmblood horses. They administered a single dose of harpagoside at a rate of 5 mg/kg body mass (in Trial 1) and 10 mg/kg body mass (in Trial 2) via nasogastric tube. They collected blood samples over time—0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours after administration—to determine harpagoside concentrations at varying timepoints.
“We detected harpagoside in the horses’ plasma 30 minutes after it was administered, and it reached a maximum concentration an hour after being administered,” Zitterl-Eglseer said. “It could still be detected up to nine hours after being administered.”
The maximum plasma concentration was 25.59 ng/ml in Trial 1 and 55.46 ng/ml in Trial 2, reached one hour after administration, she added.
“For an anti-inflammatory drug to be appropriate for long-term treatment, it is desirable for it to be able to be taken orally, to have a rapid onset of action followed by long duration of action, and to have good therapeutic effect and no or few side effects,” Zitterl-Eglseer said. “Understanding pharmacokinetic parameters helps us determine these factors. Through understanding how a body—in this case the equine body—responds to a drug, we can then use data from in vitro assays and clinical studies to develop dosage regimens and provide information for clinical treatment.”
The research team found no evidence of secondary metabolism of harpagoside in the liver. Its rapid absorption into the bloodstream is also an indicator that it is likely to have a rapid effect on the equine patient, Zitterl-Eglseer said.
And, “in our study, treatment of horses with Harpagophytum extract did not cause any clinically detectable side effects such as gastrointestinal irritation,” she said.
An increasing number of in vitro studies have confirmed devil’s claw’s anti-inflammatory, antioxidative, and analgetic properties, but to the best of the authors´ knowledge this study was the first that presented substantive pharmacokinetic data for harpagoside. They concluded that, “devil’s claw is a safe drug and well-tolerated on oral administration route,” Zitterl-Eglseer said.
The study, “Pharmacokinetics of harpagoside in horses after intragastric administration of a Devil’s claw (Harpagophytum procumbens) extract,” was published in the Journal of Veterinary Pharmacology and Therapeutics.