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Title: Bioavailability, Pharmacokinetics and Tissue Distribution of P57AS3 (P57) from Hoodia gordonii Mouse Model

Author
item MADGULA, VAMSI L.M. - University Of Mississippi
item ASHFAQ, MOHAMMAD - University Of Mississippi
item WANG, YAN-HONG - University Of Mississippi
item AVULA, BHARATHI - University Of Mississippi
item KHAN, IKHLAS - University Of Mississippi
item WALKER, LARRY - University Of Mississippi
item KHAN, SHABANA - University Of Mississippi

Submitted to: Biopharmaceutics and Drug Disposition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/19/2010
Publication Date: 7/29/2010
Citation: Madgula, V., Ashfaq, M.K., Wang, Y., Avula, B., Khan, I.A., Walker, L.A., Khan, S.I. 2010. Bioavailability, Pharmacokinetics and Tissue Distribution of P57AS3 (P57) from Hoodia gordonii Mouse Model. Biopharmaceutics and Drug Disposition. DOI http://dx.doi.org/10.10ee/S-1055-1249818.

Interpretive Summary: This manuscript describes in vivo bioavailability and pharmacokinetics of an oxypregnane steroidal glycoside (P57 ) which is claimed to be responsible for the diet suppressing activity of the preparations of the plant Hoodia gordonii used as a dietary supplement for weight loss. No report was available for in vivo bioavailability and tissue distribution of this molecule. The study was done in mouse model. P57 showed moderate bioavailability, and it was eliminated rapidly from the tissues. Upon intravenous administration the level of tissue distribution was highest in the kidney followed by the liver and brain. Upon oral administration, P57 was not detected in the brain and a very low concentration was seen in intestine, kidney and liver.

Technical Abstract: P57AS3, an oxypregnane steroidal glycoside (P57) is known to be responsible for the diet suppressing activity of Hoodia gordonii, a dietary supplement used for weight loss. In this study, bioavailability, pharmacokinetics and tissue distribution of P57 was determined in CD1 female mice after administration of a single dose of enriched methanolic extract of Hoodia gordonii (equivalent to a dose of 25mg of P57/kg) by oral gavage or a single dose of purified P57 (25mg/kg) intravenously. The level of P57 in plasma and tissues (brain, liver, kidney and intestine) was determined by UPLC-MS. After oral administration of Hoodia extract, the peak plasma level of P57 was achieved in 0.6 h. Upon intravenous administration, plasma clearance rate (CL) of P57 was 1.09 L/h/kg. P57 was rapidly distributed and eliminated from the tissues within 4 hours. The level of tissue distribution was highest in the kidney (C0=17.5 µg/mg) followed by liver (C0=13.3 µg/mg) and brain (C0=7.8 µg/mg). Upon oral administration, P57 was not detected in brain and a very low concentration was seen in intestine (Cmax=0.42 µg/mg), kidney (Cmax=0.25 µg/mg) and liver (Cmax=0.09 µg/mg). Tissue/plasma ratio was 0.33 for brain, 0.57 for liver and 0.75 for kidney with IV route and the ratio was 0.11 for intestine, 0.02 for liver and 0.04 for kidney with oral route. The half - life of elimination phase (t1/2 k10) was similar with both the routes. The oral bioavailability (%F) was 47.5% and the half - life of absorption phase (t1/2 k01) was 0.13 h with oral route. In conclusion, P57 showed moderate bioavailability and it was eliminated rapidly.