Transporter‑mediated drug‑drug interactions involving poly (ADP‑ribose) polymerase inhibitors (Review)

by Selleckchem | Apr 01 2023

Poly (ADP ribose) polymerase (PARP) inhibitors are novel targeted anticancer agents that have been widely used in patients with cancer, particularly in patients with breast-related cancer antigen 1/2 mutations. PARP inhibitors are administered orally and have been associated with improved efficacy and toxicity profiles when compared to conventional chemotherapy agents; this improvement is convenient and results in good compliance among patients with cancer. However, as PARP inhibitors are administered long-term and frequently concomitantly with other therapeutic agents, the risk of drug-drug interactions (DDIs) is increasing. Transporters are widely expressed in numerous types of tissue, where they have crucial roles in the membrane transport of several drugs. An alteration in the activity and expression of transporters may change the drug pharmacokinetics (PKs) and cause DDIs. As the five PARP inhibitors (olaparib, niraparib, rucaparib, talazoparib and veliparib) are transporter substrates, inhibitors or inducers, the potential transporter-mediated DDIs with the use of PARP inhibitors should be taken into consideration when co-administered with other agents. The present review focused on recent findings on transporter-mediated DDIs with PARP inhibitors to provide specific recommendations for reducing the occurrence of undesired DDIs.

Comments：

PARP inhibitors are a promising class of targeted anticancer agents that have shown improved efficacy and toxicity profiles in patients with breast-related cancer antigen 1/2 mutations. However, the long-term administration of PARP inhibitors and their frequent co-administration with other therapeutic agents increases the risk of drug-drug interactions (DDIs).

Transporters play a crucial role in the membrane transport of several drugs and alterations in their activity and expression may change the drug pharmacokinetics (PKs) and cause DDIs. As PARP inhibitors are transporter substrates, inhibitors or inducers, it is essential to consider potential transporter-mediated DDIs when co-administering PARP inhibitors with other agents.

Recent findings suggest that co-administration of PARP inhibitors with certain transporter substrates or inhibitors may result in clinically significant DDIs. For instance, co-administration of olaparib with P-glycoprotein (P-gp) substrates, such as digoxin, may increase the plasma concentration of digoxin and increase the risk of toxicity. Similarly, co-administration of niraparib with organic anion transporting polypeptide 1B1/1B3 (OATP1B1/1B3) substrates, such as statins, may increase the plasma concentration of statins and increase the risk of myopathy.

To reduce the occurrence of undesired DDIs, healthcare providers should consider the potential transporter-mediated DDIs when co-administering PARP inhibitors with other agents. In some cases, dose adjustments may be necessary to avoid drug toxicity or suboptimal efficacy. It is also important to monitor patients for adverse drug reactions and adjust the treatment regimen accordingly.

In summary, transporter-mediated DDIs with PARP inhibitors should be taken into consideration when co-administered with other therapeutic agents. Healthcare providers should be aware of potential interactions and monitor patients for adverse reactions to optimize the treatment regimen.