Journal of Bioequivalence & Bioavailability

Impact of glucocorticoids on the bioavailability and metabolism of abiraterone and calcitriol

6^th World Congress on Bioavailability & Bioequivalence: BA/BE Studies Summit

August 17-19, 2015 Chicago, USA

Subrata Deb, Mohamed Ben-Eltriki, Mei Y Chin, Hans Adomat and Emma S Tomlinson Guns

Scientific Tracks Abstracts: J Bioequiv Availab

Abstract:

Glucocorticoids, primarily dexamethasone and prednisone, are routinely used in the cancer treatment regimens to minimize
chemotherapy-induced nausea and vomiting, and to suppress inflammation. Interestingly, these corticosteroids are the agonists
of glucocorticoid receptor and pregnane X receptor that regulate cytochrome P450 3A4 (CYP3A4) expression in humans and
rodents. Since numerous anticancer agents (e.g. abiraterone, docetaxel) and chemopreventive agents (e.g. calcitriol, the biologically
active vitamin D3) are substrates of CYP3A4 enzyme, glucocorticoids have the potential to alter the metabolism and bioavailability
of anticancer agents. The effects of dexamethasone on the bioavailability of abiraterone (a steroidogenesis inhibitor) were evaluated
by treating adult CD-1 mice with dexamethasone dissolved in 50% ethanol at a dosage of 80 mg/kg/day for three consecutive days
by intraperitoneal injection. On the fourth day morning, a single dose of abiraterone (180 mg/kg) was administered by oral gavage,
followed by collection of blood through tail bleeding method in time intervals between 0.5-24 hrs. Serum abiraterone levels in
vehicle- or dexamethasone-treated mice were analyzed by an LC-MS/MS assay using deuterated testosterone as the internal standard.
Estimation of peak serum concentration, area under the curve and serum half-life suggests that dexamethasone significantly reduced
the bioavailability and increased elimination of abiraterone. Similarly, dexamethasone, but not prednisone, stimulated the metabolism
of calcitriol in mouse liver. In conclusion, the results from our laboratory suggest that dexamethasone in cancer treatment regimens
may alter the serum levels of anticancer agents and this may reflect in the recent preference of prednisone over dexamethasone as an
adjuvant therapy.

Biography :

Subrata Deb received his PhD from The University of British Columbia (2009) and Postdoctoral fellowship from Vancouver Prostate Centre (2011). His areas of expertise
and interests include cytochrome P450-mediated disposition of drugs and chemopreventive agents. Currently, he is an Assistant Professor in the Department of
Biopharmaceutical Sciences, Roosevelt University College of Pharmacy (IL, USA). He has published more than 10 papers in reputed journals and currently serves in
editorial boards and as reviewer for several journals of repute.