Investigations on the pharmacokinetic properties of Harpagophytum extractsand their effects on eicosanoid biosynthesis in vitro and ex vivo

Purpose: Harpagophytum extract and its marker substance harpagoside were sh own to exert antiinflammatory effects by interacting with the eicosanoid bi osynthesis. In this study, different Harphagophytum extracts were tested wi th respect to inhibition of leukotriene and thromboxane biosynthesis in vit ro and ex vivo. In addition, pharmacokinetic parameters of Harpagophytum ex tracts were investigated in vivo. Methods and Subjects: Different fractions of Harpagophytum extracts were te sted in vitro in human whole blood samples for effects on basal and ionopho re A23187-stimulated cysteinyl-leukotriene (Cys-LT) and thromboxane synthes is. Furthermore, in 3 independent studies with different numbers of human m ale volunteers, a Harpagophytum extract was administered orally and tested in whole blood samples for Cys LT and thromboxane B-2 (TXB2) biosynthesis a nd for the determination of pharmacokinetic parameters of harpagoside. Results: The special Harpagophytum extract WS1531 had a stronger inhibitory effect on ionophore A23187-stimulated Cys-LT levels compared with pure har pagoside or other extract fractions. Fractions without harpagoside had no p ronounced inhibitory effect. When Cys-LT levels were measured after oral in take of Harpagophytum extract, a biphasic but dose-independent decrease of 28% and 58%, respectively, in basal Cys-LT formation was observed. Pharmaco kinetic studies with the Harpagophytum extract WS1531 showed that the maxim um levels of plasma harpagoside were reached after 1.3 to 2.5 hours. A line ar relationship between dose and the first maximal concentration (C-max) or area under the curve (AUC) (0-1)/AUC(0-infinity) was observed. Conclusions: Our observations strongly indicate a close relation between se rum harpagoside levels and the inhibition of leukotriene biosynthesis.