Pharmacokinetics of harpagoside in horses after intragastric administration of a Devil's claw (Harpagophytum procumbens) extract
2019
Axmann, Sonja | Hummel, Karin | Nöbauer, Katharina | Razzazi‐Fazeli, Ebrahim | Zitterl‐Eglseer, Karin
Devil's claw is used for the treatment of inflammatory symptoms and degenerative disorders in horses since many years, but without the substantive pharmacokinetic data. 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, randomized 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 hr 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 noncompartmental model through PKSolver software. Harpagoside could be detected up to 9 hr after administration. Cₘₐₓ was found at 25.59 and 55.46 ng/ml, t₁/₂ at 2.53 and 2.32 hr, respectively, and tₘₐₓ at 1 hr in both trials. AUC₀–ᵢₙf was 70.46 and 117.85 ng hr ml⁻¹, respectively. A proportional relationship between dose, Cₘₐₓ and AUC was observed. Distribution (Vz/F) was 259.04 and 283.83 L/kg and clearance (CL/F) 70.96 and 84.86 L hr⁻¹ kg⁻¹, respectively. Treatment of horses with Harpagophytum extract did not cause any clinically detectable side effects.
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