title: 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 x 10(-6) cm/sec and 22 x 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 (IC(50) 3 microM), indicating a possibility of drug-herb/botanical interactions when products containing H. gordonii are used simultaneously with other botanicals/herbs/drugs.
authors.affiliation: National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.
authors.forename: Vamsi Lakshmi
authors.initials: VL
authors.lastname: Madgula
authors.forename: Bharathi
authors.initials: B
authors.lastname: Avula
authors.forename: Rahul S
authors.initials: RS
authors.lastname: Pawar
authors.forename: Yatin J
authors.initials: YJ
authors.lastname: Shukla
authors.forename: Ikhlas A
authors.initials: IA
authors.lastname: Khan
authors.forename: Larry A
authors.initials: LA
authors.lastname: Walker
authors.forename: Shabana I
authors.initials: SI
authors.lastname: Khan
mesh_terms: D029062:Apocynaceae / Q000737:chemistry*; D001798:Blood Proteins / Q000378:metabolism; D018938:Caco-2 Cells; D065692:Cytochrome P-450 CYP3A Inhibitors; D005750:Gastric Juice / Q000378:metabolism; D041743:Herb-Drug Interactions; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008861:Microsomes / Q000378:metabolism; D015394:Molecular Structure; D010936:Plant Extracts / Q000493:pharmacokinetics* / Q000494:pharmacology; D011276:Pregnanediol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D001798:Blood Proteins; D065692:Cytochrome P-450 CYP3A Inhibitors; D010936:Plant Extracts; C549431:hoodigogenin A; D011276:Pregnanediol