P-glycoprotein (Pgp; ABCB1), a member of the ATP-binding cassette (ABC) superfamily, exports structurally diverse hydrophobic compounds from the cell driven by ATP hydrolysis.1 Pgp expression has been linked to the effl ux of chemotherapeutic drugs in human cancers leading to multidrug resistance. Pgp activity can also result in low oral absorption and poor brain penetration. Interaction of drugs with the Pgp may also cause an increase in toxicity of co-administered compounds.
Interaction of drugs with active transporters such as Pgp is of increasing interest to the pharmaceutical industry based, in large part, on new draft FDA guidelines requiring knowledge of whether a drug candidate is a substrate and/or inhibitor of Pgp.
The Fluorosome Company’s Fluorosome®-trans-pgp assay, together with BMG LABTECH’s FLUOstar Omega, provides a rapid, sensitive and specifi c reconstituted Pgp liposome assay system for identifi cation of compounds that interact with the transporter. The assay measures the ability of a compound to compete with a Pgp substrate for transport, and determines the IC50 value. The FLUOstar Omega’s ability to inject at the point of measurement assures that no data is lost. Up to 50 readings per second taken concurrently upon injection, provides ample data for calculation of fi rst order transport rates. Single concentration inhibition measurements can be made very rapidly, and an IC50 determination carried out in only 10 minutes thereby.
P-glycoprotein (Pgp; ABCB1), a member of the ATP-binding cassette (ABC) superfamily, exports structurally diverse hydrophobic compounds from the cell driven by ATP hydrolysis.1 Pgp expression has been linked to the effl ux of chemotherapeutic drugs in human cancers leading to multidrug resistance. Pgp activity can also result in low oral absorption and poor brain penetration. Interaction of drugs with the Pgp may also cause an increase in toxicity of co-administered compounds.