P-glycoprotein

Definition

P-glycoprotein is a membrane transport protein that plays a critical role in the efflux of drugs and other compounds out of cells. This protein is vital in influencing drug absorption, distribution, and elimination, thus significantly impacting pharmacokinetics and therapeutic efficacy.

5 Must Know Facts For Your Next Test

1. P-glycoprotein is encoded by the ABCB1 gene and is predominantly expressed in the intestinal epithelium, liver, and blood-brain barrier.
2. The activity of p-glycoprotein can lead to decreased bioavailability of certain drugs by actively pumping them out of cells before they can exert their therapeutic effects.
3. Variations in the ABCB1 gene can result in different levels of p-glycoprotein expression among individuals, influencing drug response and the risk of adverse effects.
4. Certain drugs, including many chemotherapeutic agents, can be substrates for p-glycoprotein, leading to multidrug resistance in cancer therapy.
5. In personalized medicine, understanding a patient’s p-glycoprotein expression can help tailor drug therapies to improve efficacy and reduce toxicity.

Review Questions

• How does p-glycoprotein influence drug absorption and overall pharmacokinetics?
  • P-glycoprotein impacts drug absorption by actively transporting drugs out of cells, particularly in the intestinal lining where it reduces the amount of drug that enters systemic circulation. This action can lower the bioavailability of medications, affecting their therapeutic effectiveness. Additionally, it plays a role in drug distribution and elimination by regulating how much drug remains within cells or enters organs like the liver and kidneys for excretion.
• Discuss the relationship between p-glycoprotein expression and drug resistance in cancer treatment.
  • In cancer treatment, high levels of p-glycoprotein expression in tumor cells can lead to multidrug resistance by actively effluxing chemotherapeutic agents before they can exert their intended effects. This mechanism reduces the concentration of these drugs within cancer cells, making treatments less effective. Consequently, understanding the expression levels of p-glycoprotein in tumors can help guide therapy choices and potentially lead to the development of strategies to inhibit its function.
• Evaluate how genetic variations in the ABCB1 gene affect individual responses to medication involving p-glycoprotein.
  • Genetic variations in the ABCB1 gene, which encodes p-glycoprotein, can significantly affect individual responses to medications. These polymorphisms may result in varying levels of protein expression or activity among patients, leading to differences in drug metabolism and efficacy. For example, individuals with certain alleles may experience higher drug concentrations due to reduced efflux activity, while others may have increased drug clearance. Such insights are crucial for personalizing therapy to enhance treatment outcomes and minimize adverse effects.

Related terms

ABC Transporters: ATP-binding cassette (ABC) transporters are a large family of proteins that utilize ATP to transport various molecules across cellular membranes, including drugs and xenobiotics.

Drug Resistance: Drug resistance refers to the reduction in effectiveness of a medication in treating a disease or condition, often caused by the overexpression of efflux transporters like p-glycoprotein.

Pharmacokinetics: Pharmacokinetics is the study of how drugs are absorbed, distributed, metabolized, and excreted by the body, closely related to the function of transport proteins like p-glycoprotein.