The Impact of P-Glycoprotein on Opioid Analgesics: What’s the Real Meaning in Pain Management and Palliative Care?

Abstract

Opioids are widely used in cancer and non-cancer pain management. However, many transporters at the blood–brain barrier (BBB), such as P-glycoprotein (P-gp, ABCB1/MDR1), may impair their delivery to the brain, thus leading to opioid tolerance. Nonetheless, opioids may regulate P-gp expression, thus altering the transport of other compounds, namely chemotherapeutic agents, resulting in pharmacoresistance. Other kinds of painkillers (e.g., acetaminophen, dexamethasone) and adjuvant drugs used for neuropathic pain may act as P-gp substrates and modulate its expression, thus making pain management challenging. Inflammatory conditions are also believed to upregulate P-gp. The role of P-gp in drug–drug interactions is currently under investigation, since many P-gp substrates may also act as substrates for the cytochrome P450 enzymes, which metabolize a wide range of xenobiotics and endobiotics. Genetic variability of the ABCB1/MDR1 gene may be accountable for inter-individual variation in opioid-induced analgesia. P-gp also plays a role in the management of opioid-induced adverse effects, such as constipation. Peripherally acting mu-opioid receptors antagonists (PAMORAs), such as naloxegol and naldemedine, are substrates of P-gp, which prevent their penetration in the central nervous system. In our review, we explore the interactions between P-gp and opioidergic drugs, with their implications in clinical practice.

Chitosan in Oral Drug Delivery Formulations: A Review

“…P-gp is a membrane transporter protein found in the gastrointestinal tract that actively pumps drugs out of the enterocytes, thereby limiting their absorption and bioavailability. Nanoformulations such as polymeric nanoparticles and lipid-based carriers gained significant attention as oral drug delivery systems due to their ability to improve drug solubility, stability, and target-specific delivery [ 71 , 72 ]. P-gp inhibitors, when co-administered with nanoformulated drugs, inhibit the efflux activity of P-gp, allowing for increased drug absorption and improved therapeutic outcomes.…”

How to use opioid analgesics effectively and safely. Individual choice of the opioid in patients with cancer pain from the perspective of 2022

“…wchłanianie leków i innych substancji z przewodu pokarmowego, ich przenikanie przez barierę krew-mózg oraz eliminację z organizmu z moczem lub żółcią. GpP odgrywa ważną rolę w dystrybucji niektórych opioidów, takich jak morfina, fentanyl i metadon oraz ich aktywnych metabolitów (jak M3G, M6G i norbuprenorfina) [19,77,78]. GpP reguluje poziom opioidów -substratów gpP w OUN, co warunkuje ich ośrodkowe działanie.…”

The influence of COMT and ABCB1 gene polymorphisms on sufentanil analgesic effect for postoperative pain in children with fracture

“…[5] ATP-binding cassette transporter B1 (ABCB1) transports various opioid analgesics across the blood-brain barrier. [6,7] Previous studies have demonstrated the association between SNPs in the COMT and ABCB1 genes and interindividual differences in pain perception and response to analgesics, [8][9][10] with a focus on chronic pain and adult patients, while research on the relationship between these gene SNPs and acute postoperative pain in pediatric patients is limited. Therefore, this study aims to investigate the correlation between SNPs in the COMT and ABCB1 genes and individual differences in postoperative analgesia with sufentanil in children with fractures, providing a theoretical basis for individualized analgesic therapy in pediatric patients.…”