All-trans-retinoic acid modulation of drug-metabolizing enzyme activities: investigation with selective metabolic drug probes

Cancer Chemotherapy and Pharmacology
A AdedoyinD L Trump

Abstract

All-trans-retinoic acid (ATRA) is a retinoid analogue that has been shown to be effective in acute promyelocytic leukemia. It is currently being investigated for efficacy in the treatment and prevention of various types of cancer. One of the factors limiting its use is the observed increase in ATRA clearance and elimination which occurs shortly after treatment is started, leading to reduced levels of drug in the body and loss of effectiveness. ATRA efficacy may be enhanced if this autoinduction of metabolism can be overcome, for example through the inhibition of the activity of the induced specific metabolizing enzyme(s). This requires the identification of this induced enzyme(s) and development of approaches to selectively inhibit its activity. In the course of a phase II evaluation of ATRA in prostate cancer, we investigated the activities of five specific cytochrome P450 (CYP) (CYPs 1A2, 2C19, 2D6, 2E1 and 3A4) and N-acetyltransferase enzymes using a newly developed five-drug cocktail involving caffeine, mephenytoin, debrisoquine, chlorzoxazone and dapsone respectively. Enzyme activities were assessed in 17 patients with hormone-refractory prostate cancer before the initiation of ATRA therapy, after 14 days of continuous ATR...Continue Reading

Citations

Oct 16, 1999·Biochimica Et Biophysica Acta·J L Napoli
Oct 25, 2002·Journal of Women's Health & Gender-based Medicine·Marietta Anthony, Mary J Berg
Jun 8, 2002·Pharmacogenomics·Peter Meisel
Jan 1, 2007·Indian Journal of Urology : IJU : Journal of the Urological Society of India·Vivek Vijjan, Deepak Dubey
Nov 6, 2012·Expert Review of Clinical Pharmacology·Janne Hukkanen
May 16, 2009·Expert Opinion on Drug Metabolism & Toxicology·Laura MacDonaldBrian C Foster
May 9, 2002·Drug Metabolism Reviews·Slobodan Rendic
Feb 21, 2006·British Journal of Clinical Pharmacology·Julie A SimpsonSteve Ward
Apr 2, 2017·In Vitro Cellular & Developmental Biology. Animal·Dong LiBichun Li
Apr 5, 2018·Leukemia & Lymphoma·Robert L RednerDaniel E Johnson
Jan 30, 2004·Journal of Clinical Pharmacology·Honghui ZhouJames F McLeod
Jun 20, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Thorir D BjornssonUNKNOWN FDA Center for Drug Evaluation and Research (CDER)
Jan 23, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mohamed R AbdelaalHesham Haffez
Oct 29, 2020·Archives of Toxicology·Jukka HakkolaOlavi Pelkonen

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