Approaches to minimize the effects of P‐glycoprotein in drug transport: A review

Abstract

P-glycoprotein (P-gp) is a transporter protein that is come under the ATP binding cassette family of proteins. It is situated on the surface of the intestine epithelium, where P-gp substrate binds to the transporter and is pumped into the intestine lumen by the ATP-driven energy-dependent process. In this review, we summarize the role of the P-gp efflux transporter situated on the intestine, the clinical importance of P-gp related drug interactions, and approaches to minimize the effect of P-gp in drug transport. This review also focuses on the impact of P-gp on the bioavailability of the orally administered drug. Many drug's oral bioavailabilities can improve by concomitant use of P-gp inhibitors. Multidrug resistance are reduced by using some naturally occurring compounds obtained from plants and several synthetic P-gp inhibitors. Formulation strategies, one of the most important approaches to mimic the P-gp transporter's action, finally enhancing the oral bioavailability of the drug by inhibiting its P-gp efflux. Vitamin E TPGS, Gelucire 44/14 and other pharmaceutical/formulation excipients inhibit the P-gp efflux. A prodrug approach might be a useful strategy to overcome drug resistance.Prodrug helps to enhance the solubility or alter the pharmacokinetic properties but does not diminish the pharmacological action.

Multidrug Resistance of Cancer Cells and the Vital Role of P-Glycoprotein

“…Black pepper contains the flavonoid piperine. It has the capacity to function as a natural inhibitor of P-gp and CYP34A when co-administered and can boost the therapeutic efficacy of medications [1]. To induce this effect, the piperine dosage should be optimal and reach the minimal therapeutic concentration.…”

“…The phenomenon known as drug resistance is responsible for the decrease in the restorative rate of most diseases as well as the loss in the therapeutic efficacy of most of the Life 2022, 12, 897. https://doi.org/10.3390/life12060897 https://www.mdpi.com/journal/life anticancer medications [1]. Treatment resistance is found not only to a single chemotherapeutic drug but to a diverse set of structurally and functionally distinct medicines.…”

Blood-brain barrier dysfunction in bipolar disorder: Molecular mechanisms and clinical implications

“…One significant way the BBB interacts with pharmacological agents is through P-glycoprotein (P-gp), a transmembrane protein expressed on BMECs that functions as a drug efflux pump helping to eliminate potentially dangerous substances. Interestingly, drugs utilized in BD are known to have varying effects on P-gp function ( Husain et al., 2022 ). Notably, positron emission tomography studies in psychiatric patients have found increased P-gp function in the BBB ( de Klerk et al., 2010 ).…”

The role of the efflux transporter, P‐glycoprotein, at the blood–brain barrier in drug discovery

“…Whilst the Caco2 cells offer an efficient model to predict the passive permeability and active efflux in the intestine, the MDR1-MDCK cells express limited enzymes and basal transporter activity and hence more readily mimic the BBB (Colclough et al, 2019;Husain et al, 2022).…”