Evaluation of inhibitory potencies for compounds inhibiting P-glycoprotein but without maximum effects

• Verfasst von: Weiß, Johanna [VerfasserIn]
• Verfasst von: Haefeli, Walter E. [VerfasserIn]
• Titel: Evaluation of inhibitory potencies for compounds inhibiting P-glycoprotein but without maximum effects
• Titelzusatz: F2 values
• Verf.angabe: Johanna Weiss, Walter Emil Haefeli
• E-Jahr: 2006
• Jahr: January 25, 2006
• Umfang: 5 S.
• Teil: volume:34
• Teil: year:2006
• Teil: number:2
• Teil: pages:203-207
• Teil: extent:5
• Fussnoten: Gesehen am 17.05.2021 ; Im Titel ist "2" tiefgestellt
• Titel Quelle: Enthalten in: Drug metabolism and disposition
• Ort Quelle: Bethesda, Md. : ASPET, 1973
• Jahr Quelle: 2006
• Band/Heft Quelle: 34(2006), 2, Seite 203-207
• ISSN Quelle: 1521-009X
• DOI: doi:10.1124/dmd.105.007377
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1757913734

Abstract

In cell culture systems with aqueous buffers, concentration-response curves to lipophilic inhibitors are difficult to establish because plateau effects (Imax) are often not reached because of limited drug solubility. Consequently, the inhibitory potency of a compound will not be definable using IC50 values (concentration exerting 50% of Imax). Since alternative potency measures f2 values, the concentrations required to double baseline signals have been proposed. Using both methods, we reevaluated the concentration-response curves of calcein assays with 78 compounds in three different cell culture systems and found a close correlation between both methods (rs = 0.93-0.99, p ≤ 0.0028). These findings suggest that f2 values are a valuable alternative to define rank orders of highly lipophilic inhibitors as a basis for the prediction of pharmacological interaction properties in clinical settings. Although it was only tested for inhibition of P-glycoprotein, it seems likely that this method may be transferred to other assays with other proteins.