Bioavailability of Tyrosine Kinase Inhibitors

An Added Component of Assessment

Kristine Deano Abueg, RN, MSN, OCN, CBCN


Clin J Oncol Nurs. 2014;18(6):714-716. 

In This Article

P-glycoprotein Drug Interactions

P-gp is located on the cell membrane of various tissues, including the intestines and liver. As an efflux transporter, P-gp is one of the enzymes responsible for clearing drugs and toxins from cells. The role of P-gp in normal tissue is likely to protect susceptible organs from toxic compounds by limiting their aggregation in the cell. However, P-gp can also efficiently clear aggregated anticancer agents out of the target cell. In vivo studies have reported an overexpression of P-gp, which suggests that cancer cells have an efficient mechanism to clear antineoplastic drugs from themselves (Lin & Yamazaki, 2003).

Many oral agents are known substrates of P-gp and, therefore, are affected by alterations to the function of P-gp. Impeding the ability of P-gp to effectively clear drugs or toxins will result in intracellular accumulation. Conversely, acceleration of the P-gp enzyme will deplete intracellular drug concentration. Providers should be aware of the potential interaction between P-gp inhibitors and substrates.

Atorvastatin is a known inhibitor of P-gp, whereas erlotinib is a known substrate. Atorvastatin will interact with P-gp, slowing the efflux activity of P-gp and causing an accumulation of concomitant erlotinib within the cell. This will likely result in a dosing greater than the target dosing (FDA, 2011). Figure 1 lists examples of P-gp substrates and inhibitors.

Figure 1.

Examples of P-Glycoprotein Substrates and Inhibitors
Note. Based on information from U.S. Food and Drug Administration, 2011; van Leeuwen et al., 2014.