Publications by authors named "R L O'Connor-Semmes"
Linerixibat, an oral small-molecule ileal bile acid transporter inhibitor under development for cholestatic pruritus in primary biliary cholangitis, was designed for minimal absorption from the intestine (site of pharmacological action). This study characterized the pharmacokinetics, absorption, metabolism, and excretion of [C]-linerixibat in humans after an intravenous microtracer concomitant with unlabeled oral tablets and [C]-linerixibat oral solution. Linerixibat exhibited absorption-limited flip-flop kinetics: longer oral versus intravenous half-life (6-7 hours vs.
View Article and Find Full Text PDFBackground: GSK2849330, an anti-HER3 monoclonal antibody that blocks HER3/Neuregulin 1 (NRG1) signaling in cancer cells, is engineered for enhanced antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. This phase I, first-in-human, open-label study assessed the safety, pharmacokinetics (PK), pharmacodynamics, and preliminary activity of GSK2849330 in patients with HER3-expressing advanced solid tumors.
Patients And Methods: Patients with various tumor types were prospectively selected for HER3 expression by immunohistochemistry; a subset was also screened for NRG1 mRNA expression.
Article Synopsis
- The study evaluated the safety and effects of remogliflozinetabonate, an SGLT2 inhibitor, combined with metformin in patients with type 2 diabetes mellitus (T2DM) to help lower their glycemic index and avoid complications.
- Conducted as a randomized, double-blind study with 50 subjects, participants received either remogliflozinetabonate (at 500 mg or 750 mg) or a placebo alongside their stable metformin regimen for 13 days.
- Results showed that the combination was well tolerated with no serious adverse events or increased lactic acid levels, and it did not impact the pharmacokinetics of metformin during the study period.
Rearranged during transfection (RET), a neuronal growth factor receptor tyrosine kinase, regulates the development of sympathetic, parasympathetic, motor, and sensory neurons in the enteric nervous system. The intended site of action for GSK3352589 is intestinal tissues. GSK3352589 is an RET kinase inhibitor that was administered in double-blind, randomized, placebo-controlled single-dose (SD) and repeat-dose (RD) studies in healthy subjects to investigate its safety/tolerability and pharmacokinetics.
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