Impact of fedratinib on the pharmacokinetics of transporter probe substrates using a cocktail approach.

Introduction: Fedratinib, an oral, selective Janus kinase 2 inhibitor, has been shown to inhibit P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP) 1B1, OATP1B3, organic cation transporter (OCT) 2, and multidrug and toxin extrusion (MATE) 1 and MATE2-K in vitro. The objective of this study was to evaluate the influence of fedratinib on the pharmacokinetics (PK) of digoxin (P-gp substrate), rosuvastatin (OATP1B1/1B3 and BCRP substrate), and metformin (OCT2 and MATE1/2-K substrate).

Methods: In this nonrandomized, fixed-sequence, open-label study, 24 healthy adult participants received single oral doses of digoxin 0.

A randomised trial comparing the pharmacokinetics and safety of the biosimilar CT-P6 with reference trastuzumab.

Purpose: Access to trastuzumab, a valuable anti-cancer treatment, can be limited by cost. The primary aim of this study was to evaluate and compare the PK profiles of CT-P6, a biosimilar of trastuzumab, and US-licensed reference trastuzumab (Herceptin) in healthy subjects. Secondary study aims included comparison of the safety and immunogenicity of CT-P6 and reference trastuzumab in these subjects.

The Pharmacokinetics of the CYP3A Substrate Midazolam After Steady-state Dosing of Delafloxacin.

Purpose: Delafloxacin is a novel anionic fluoroquinolone in Phase III development for the treatment of serious skin infections. The objective of this study was to evaluate the effects of delafloxacin on the pharmacokinetics of midazolam, a cytochrome P450 (CYP) 3A substrate.

Methods: CYP3A activity using midazolam as a probe was assessed before and after multiple doses of delafloxacin to reach steady state.