PharmPK Discussion - Arishel Newsletter: No 3, September 23, 2007

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On 28 Sep 2007 at 17:04:56, Clerk Maxwell (clerkmaxwell.aaa.hotmail.com) sent the message


Topotecan oral bioavailability increased dramatically by inhibiting BCRP

Topotecan, an anti-cancer drug, is being administered IV, since its
oral absolute bioavailability (F) is 42 +/- 13 %.  This relatively
low value for F is primary due to the effect of the gut efflux
transporter breast cancer resistance protein (BCRP).  By blocking the
effect of BCRP with elacridar, the oral absolute bioavailability of
topotecan increases to 100%.  The reference cited below deals with
this phenomenon:

A phase I, randomized, open-label, parallel-cohort, dose-finding
study of elacridar (GF120918) and oral topotecan in cancer patients.
Clin Cancer Res, 2007 Jun 1;13(11):3276-85.
Kuppens IE, Witteveen EO, Jewell RC, Radema SA, Paul EM, Mangum SG,
Beijnen JH, Voest EE, Schellens JH.

Harold Boxenbaum, Ph.D.
Pharmacokinetics Consultant
Arishel Inc.
14621 Settlers Landing Way
North Potomac, MD 20878-4305
(P) 301-424-2806
(F) 301-424-8563
harold.-at-.arishel.com
www.arishel.com

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