Co-administration of phytochemicals and anti-melanoma drugs: Mechanisms, metastasis prevention, and regulatory challenges

Huner I. B., Kasim Kirac M., ÜLGEN Ş. K.

Pharmacological Research - Natural Products, cilt.10, 2026 (Scopus)

Özet

This review focuses on the pharmacokinetic effects of phytochemicals or foods on drugs currently used for melanoma therapy or those with the potential to prevent melanoma metastasis. The pharmacokinetic effects of piperine, Eurycoma longifolia, and garlic co-administered with propranolol, as well as carvone and orange juice co-administered with ivermectin, are investigated, along with the impact of imperatorin on dabrafenib pharmacokinetic parameters. Upon research suggesting that platelet inhibition may be useful for preventing melanoma metastases, the pharmacokinetic parameters of ticagrelor are examined in the context of grapefruit juice consumption or the administration of conventional anticancer drugs. Across the reviewed studies, piperine and garlic increased propranolol bioavailability up to twofold, while imperatorin elevated dabrafenib plasma exposure by more than threefold through CYP3A4 inhibition. Conversely, Eurycoma longifolia and orange juice decreased drug absorption, illustrating the dual modulatory potential of dietary agents on melanoma therapies. The possible drawbacks and advantages of these synergistic phytochemical-drug combinations are discussed, along with regulatory and ethical challenges. The mechanistic and molecular aspects of reshaping therapeutic dynamics upon coadministration of drugs and phytochemicals are deliberated. Precision medicine and phytochemical delivery technologies are highlighted.