Transporters in Drug Development: 2018 ITC Recommendations for Transporters of Emerging Clinical Importance

This white paper provides updated International Transporter Consortium (ITC) recommendations on transporters that are important in drug development following the 3rd ITC workshop. New additions include prospective evaluation of organic cation transporter 1 (OCT1) and retrospective evaluation of organic anion transporting polypeptide (OATP)2B1 because of their important roles in drug absorption, disposition, and effects. For the first time, the ITC underscores the importance of transporters involved in drug-induced vitamin deficiency (THTR2) and those involved in the disposition of biomarkers of organ function (OAT2 and bile acid transporters)

Stability Assessment Of Donepezil Hydrochloride Using Validated RP-HPLC Method

ABSTRACT Stability of donepezil hydrochloride was investigated using stability indicating high performance liquid chromatography (HPLC) utilizing C-18 column and mobile phase containing methanol, acetate buffer (pH 4.25) and triethylamine in ratio of 50:50:0.5 at flow rate of 1 ml min -1 . Peaks of donepezil and degradation products were well resolved at retention times < 7 min. Stability was performed in 1N hydrochloric acid, 2N sodium hydroxide, 6 % hydrogen peroxide, neutral, photolytic and dry heat conditions. Fast hydrolysis was seen in alkaline condition as compared to oxidative and neutral conditions. Study of degradation kinetics was carried out in 2N sodium hydroxide, 6 % hydrogen peroxide and neutral solutions at 4

Identification of Novel Breast Cancer Resistance Protein (BCRP) Inhibitors by Virtual Screening

Breast cancer resistance protein (BCRP; ABCG2) is an efflux transporter that plays an important role in multidrug resistance to antineoplastic drugs. The identification of drugs as BCRP inhibitors could aid in designing better therapeutic strategies for cancer treatment and will be critical for identifying potential drug–drug interactions. In the present study, we applied ligand-based virtual screening combined with experimental testing for the identification of novel drugs that can possibly interact with BCRP. Bayesian and pharmacophore models generated with known BCRP inhibitors were validated with an external test set. The resulting models were applied to predict new potential drug candidates from a database with more than 2000 FDA-approved drugs. Thirty-three drugs were tested <i>in vitro</i> for their inhibitory effects on BCRP-mediated transport of [³H]-mitoxantrone in MCF-7/AdrVp cells. Nineteen drugs were identified with significant inhibitory effect on BCRP transport function. The combined strategy of computational and experimental approaches in this paper has suggested potential drug candidates and thus represents an effective tool for rational identification of modulators of other proteins

Transporters in Drug Development: 2018 ITC Recommendations for Transporters of Emerging Clinical Importance

This white paper provides updated International Transporter Consortium (ITC) recommendations on transporters that are important in drug development following the 3rd ITC workshop. New additions include prospective evaluation of organic cation transporter 1 (OCT1) and retrospective evaluation of organic anion transporting polypeptide (OATP)2B1 because of their important roles in drug absorption, disposition, and effects. For the first time, the ITC underscores the importance of transporters involved in drug-induced vitamin deficiency (THTR2) and those involved in the disposition of biomarkers of organ function (OAT2 and bile acid transporters)