Saquinavir Subject To MDR Pump Clearance

Researchers from Stanford University in California, USA, have foundthat P-glycoprotein, a protein central to many forms of multidrug resistance in cancer, may also prevent the absorption of Roche's HIV protease inhibitor Invirase (saquinavir).

Saquinavir was the first protease inhibitor to reach the market, but has suffered from poor absorption. Roche is working to improve the formulation. If the Stanford researchers are correct, giving compounds which block the PG pump could improve absorption.

The researchers investigated whether PG was affecting saquinavir after observing that the drug was metabolized by the cytochrome P450 enzyme system - P450 and PG often target similar compounds. They used two cancer cell lines, one expressing PG and one that did not, and compared their ability to withstand saquinavir challenge. They found that the PG-expressing cells survived at much higher concentrations of the drug.