Talazoparib blood-brain barrier

Some clinical studies have shown that talazoparib (Talazoparib) has a significant propensity for MDR1 efflux and may limit transport across the blood-brain barrier, which may explain the loss of talazoparib-mediated temozolomide sensitization in orthotopic versus ectopic GBM xenografts. The blood-brain barrier is a special structure formed by the tight connection of vascular endothelial cells. Its main function is to restrict external substances from entering the brain tissue and protect the brain from harmful substances.

PolyADP-ribose polymerase (PARP) inhibitors, including talazopanib, enhance the efficacy of temozolomide in multiple tumor types; however, talazopanib-mediated sensitization has not been evaluated in orthotopic glioblastoma (GBM) models. This study evaluated tazopanide and temozolomide in a clinically relevant GBM model. Talazopanib at 1-3 nmol/L sensitized T98G, U251, and GBM12 cells to temozolomide, and extracorporeal circulation treatment with talazopanib (0.15 mg/kg, twice daily) combined with low-dose temozolomide (5 mg/kg, twice daily) enhanced DNA damage signaling and G2-M phase arrest and was well tolerated. However, in corresponding orthotopic xenografts, talazopanib/temozolomide did not increase survival in addition to temozolomide alone.

The original drug of talazopanib has not yet been marketed in China, so it has not been included in medical insurance. The original drug specification of talazopanib listed overseas is 0.25mg*30 capsules, and the price per box may be around RMB 10,000 (the price may fluctuate due to exchange rate effects), which is relatively expensive. There are also cheaper generics of talazopanib overseas. For example, the price of a box of 1mg*30 pills produced by a Laos pharmaceutical factory may be more than 3,000 yuan (the price may fluctuate due to the exchange rate).