Evaluation of Pharmacokinetics of Lebrikizumab in Healthy Individuals After Subcutaneous Administration Using a Prefilled Syringe or Autoinjector in a Phase 1 Randomized Study.

Purpose: Lebrikizumab is a novel, high-affinity immunoglobulin G4 monoclonal antibody that targets interleukin-13, a central mediator in atopic dermatitis (AD). In previous studies in patients with moderate-to-severe AD, lebrikizumab, administered subcutaneously via a prefilled syringe with a needle safety device (PFS-NSD), demonstrated rapid and durable dose-dependent efficacy. We assessed the pharmacokinetics and safety of lebrikizumab using either a PFS-NSD or an investigational autoinjector.

Prediction of the Renal Organic Anion Transporter 1 (OAT1)- Mediated Drug Interactions for LY404039, the Active Metabolite of Pomaglumetad Methionil.

Purpose: The objective of this work was to demonstrate that clinical OAT1-mediated DDIs can be predicted using physiologically based pharmacokinetic (PBPK) modeling.

Methods: LY404039 is a metabotropic glutamate receptor 2/3 agonist and the active moiety of the prodrug pomaglumetad methionil (LY2140023). After oral administration, pomaglumetad methionil is rapidly taken up by enterocytes via PEPT1 and once absorbed, converted to LY404039 via membrane dehydropeptidase 1 (DPEP1).

Target modulation and pharmacokinetics/pharmacodynamics translation of the BTK inhibitor poseltinib for model-informed phase II dose selection.

The selective Bruton tyrosine kinase (BTK) inhibitor poseltinib has been shown to inhibit the BCR signal transduction pathway and cytokine production in B cells (Park et al. Arthritis Res. Ther.

Safety and Efficacy of Poseltinib, Bruton's Tyrosine Kinase Inhibitor, in Patients With Rheumatoid Arthritis: A Randomized, Double-blind, Placebo-controlled, 2-part Phase II Study.

Objective: To evaluate the efficacy and safety of poseltinib (formerly LY3337641/HM71224), an irreversible covalent inhibitor of Bruton's tyrosine kinase in a 2-part, phase II trial (RAjuvenate; ClinicalTrials.gov: NCT02628028) in adults with active rheumatoid arthritis (RA).

Methods: In Part A, 36 patients with mildly active RA were randomized 1:1:1:1 to oral poseltinib 5, 10, or 30 mg or placebo once daily for 4 weeks to assess safety and tolerability.

In Vitro and Clinical Evaluations of the Drug-Drug Interaction Potential of a Metabotropic Glutamate 2/3 Receptor Agonist Prodrug with Intestinal Peptide Transporter 1.

Despite peptide transporter 1 (PEPT1) being responsible for the bioavailability for a variety of drugs, there has been little study of its potential involvement in drug-drug interactions. Pomaglumetad methionil, a metabotropic glutamate 2/3 receptor agonist prodrug, utilizes PEPT1 to enhance absorption and bioavailability. In vitro studies were conducted to guide the decision to conduct a clinical drug interaction study and to inform the clinical study design.