1.Antitubercular agent delamanid and metabolites as substrates and inhibitors of ABC and SLC transporters.
Sasabe H1, Shimokawa Y2, Shibata M2, Hashizume K3, Hamasako Y3, Ohzone Y3, Kashiyama E2, Umehara K2. Antimicrob Agents Chemother. 2016 Mar 28. pii: AAC.03049-15. [Epub ahead of print]
Delamanid (Deltyba™; OPC-67683) is the first approved drug in a novel class of nitro-dihydro-imidazooxazoles developed for the treatment of multidrug-resistant tuberculosis. Patients with tuberculosis require treatment with multiple drugs, several of which have known drug-drug interactions. Transporters regulate drug absorption, distribution and excretion; therefore, the inhibition of transport by one agent may alter the pharmacokinetics of another, leading to unexpected adverse events. Therefore, it is important to understand how delamanid affects transport activity. In the present study, the potencies of delamanid and its main metabolites as substrates and inhibitors of various transporters were evaluated in vitro. Delamanid was not transported by the efflux ATP-binding cassette (ABC) transporters P-glycoprotein (MDR1/ABCB1) and breast cancer resistance protein (BCRP/ABCG2), solute carrier (SLC) transporters, organic anion transporting polypeptides or organic cation transporter 1.
2.Bedaquiline and delamanid in tuberculosis.
Esposito S1, Bianchini S1, Blasi F2. Expert Opin Pharmacother. 2015;16(15):2319-30. doi: 10.1517/14656566.2015.1080240. Epub 2015 Aug 19.
INTRODUCTION: In recent years, a pressing need to develop new, effective and safe drugs against tuberculosis (TB) has continued. Poor adherence to a long therapeutic regimen against TB, intermittent drug use, errors in medical prescriptions, low quality of old TB drugs and ineffective TB control have led to the emergence of resistant TB.