TY - JOUR T1 - Influence of Antipsychotic, Antiemetic, and Ca<sup>2+</sup>Channel Blocker Drugs on the Cellular Accumulation of the Anticancer Drug Daunorubicin: P-glycoprotein Modulation JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1276 LP - 1283 VL - 295 IS - 3 AU - Safaa Ibrahim AU - James Peggins AU - Alan Knapton AU - Thomas Licht AU - Adorjan Aszalos Y1 - 2000/12/01 UR - http://jpet.aspetjournals.org/content/295/3/1276.abstract N2 - We investigated the effect of antiemetic, antipsychotic, and Ca2+ blocker drugs on the function of P-glycoprotein (Pgp) in vitro and compared inhibitory concentrations with therapeutic blood levels. Human colon adenocarcinoma (Caco-2) and human blood-brain barrier endothelial cells were transfected or transduced to express Pgp, and the uptake of rhodamine123, calcein AM, or daunorubicin was measured by flow cytometry in the presence of the drugs. NIH3T3/MDR1 cells were used for reference testing. Results of the flow cytometric studies were supported by cell proliferation and monolayer permeability studies. Thirty-five drugs are included in this study, of which 13 modulate the function of Pgp at the therapeutic blood concentration and 8 at a concentration 2 to 4 times higher. Two drugs, which block the function of Pgp only partially at therapeutic blood concentrations, blocked the function of Pgp completely if used concomitantly. Based on these in vitro experiments, we conclude that administration of several drugs that modulate the function of Pgp simultaneously may adversely affect the natural function of this efflux pump and may cause drug-induced side effects in patients. U.S. Government ER -