Devil’s claw (Harpagophytum procumbens) – Pharmacokinetics of harpagoside in horses

Devil’s claw is used for the treatment of chronic inflammatory symptoms and degenerative disorders [1] in horses since many years, but without the substantive equine pharmacokinetic data [2],[3],[4].

The pharmacokinetic parameters of harpagoside, the main active constituent of Harpagophytum procumbens DC ex Meisn., were evaluated in equine plasma after administration of Harpagophytum extract FB 8858 in an open, single-dose, two-treatment, two-period, randomised cross-over design. Six horses received a single dose of Harpagophytum extract, corresponding to 5 mg/kg BM harpagoside, and after 7 days washout period, 10 mg/kg BM harpagoside via nasogastric tube. Plasma samples at certain time points (before and 0-24 h after administration) were collected, cleaned up by solid-phase extraction and harpagoside concentrations were determined by LC-MS/MS using apigenin-7-glucoside as internal standard. Plasma concentration-time data and relevant parameters were described by non-compartmental model through PKSolver software. Harpagoside could be detected up to 9 h after administration. C_max was found at 25.59 and 55.46 ng/ml, t_1/2 at 2.53 h and 2.32 h, respectively and t_max at one hour in both trials. AUC_0-inf was 70.46 and 117.85 ng h ml^-1, respectively. A proportional relationship between dose, C_max and AUC was observed. Distribution (V_z/F) was 259.04 and 283.83 L/kg and clearance (CL/F) 70.96 and 84.86 L h^-1 kg^-1, respectively.

Treatment of horses with Harpagophytum extract did not cause any clinically detectable side effects. The knowledge of basic equine pharmacokinetics, based on the results of this study, will help to link results from in vitro assays and clinical studies and optimise therapeutic efficacy.

Fig. 1 Mean plasma concentration-time profile of harpagoside after single intragastric dosing of Harpagophytum procumbens extract FB 8858 corresponding to 5 mg/kg BM harpagoside (trial 1) and 10 mg/kg BM harpagoside (trial 2) to six horses

• References

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