Characterization of in Vitro Pharmacokinetic Properties of Hoodigogenin A from Hoodia gordonii

Abstract

This study was aimed to predict the pharmacokinetic properties of hoodigogenin A, which is the aglycone of the oxypregnane steroidal glycoside P57AS3 (P57) isolated from Hoodia gordonii. A series of in vitro assays was used to predict its gastric, intestinal and metabolic stability, intestinal and blood brain barrier (BBB) transport, protein binding and interaction with major drug metabolising enzymes. In the simulated gastric fluid, hoodigogenin A was stable (2 % degradation in 60 minutes) whereas P57 was unstable (45 % degradation in 30 minutes). In simulated intestinal fluid, P57 was degraded to an extent of 8 % in 180 minutes, while hoodigogenin A was stable. Hoodigogenin A was efficiently transported by passive diffusion across Caco-2 and MDR1-MDCK monolayers with P_app values in the range of 32 × 10⁻⁶ cm/sec and 22 × 10⁻⁶ cm/sec, respectively. The compound was metabolically unstable in human liver microsomes and S9 fractions with a CL′_int of 71 and 120 mL/min/kg, respectively and was bound to the plasma proteins to an extent of 92 %. The compound strongly inhibited CYP3A4 activity (IC₅₀ 3 µM), indicating a possibility of drug-herb/botanical interactions when products containing H. gordonii are used simultaneously with other botanicals/herbs/drugs.

Hoodia gordonii - Asclepiadaceae - hoodigogenin A - metabolic stability - CYP inhibition - intestinal and blood brain barrier transport

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