{
  "abstract": "Background and Importance Vedolizumab has emerged as a therapeutic alternative for gastrointestinal graft-versus-host disease (GI-GVHD) refractory to corticosteroids and ruxolitinib. However, optimal dosing strategies in this population remain unclear.Aim and Objectives To develop a population pharmacokinetic (popPK) model for vedolizumab in adult patients with malignant haematological neoplasms (MHN) and refractory GI-GVHD, and to propose a dosing regimen to achieve therapeutic plasma concentrations from the start of treatment.Material and Methods A prospective multidisciplinary study (January 2021–February 2025) was conducted in adults with MHN receiving vedolizumab for refractory GI-GVHD. Demographic, clinical, and biochemical data were collected. Patients received an initial 300 mg IV dose; plasma concentrations (VPC) were measured at 72 hours and subsequently as guided by the pharmacist. VPC were quantified by ELISA.The popPK model was developed using NONMEM v7.3 with the FOCEI method, and simulations were performed in R v4.3.2. The dosing required to maintain VPC >25 µg/mL (target induction level in ulcerative colitis) was estimated through deterministic simulations.Results Fifteen patients (nine females; median age 54 (18–66) years; weight 71 (40–100) kg) were included. Underlying MHN included acute myeloid leukaemia (n=7), acute lymphoblastic leukaemia (n=2), myelodysplastic syndrome (n=2), and others (n=4). Vedolizumab was used as third-line therapy in seven patients, fourth-line in three, and ≥fifth-line in five patients.A total of 70 samples (median 4 (2–10) per patient) yielded a mean (SD) VPC of 36.56 (14.97) µg/mL. A one-compartment model with first-order elimination best described the data. Volume of distribution (Vd) was 5.53 L; clearance (CL) was estimated as:CL (L/h) = 0.053 × ((BSA/1.9)^2.23) × (1 + 0.022 × (AGE–54)).Simulations suggested maintaining >25 µg/mL requires 300 mg IV at days 0, 3, and 6, followed by 300 mg every 7 days for BSA <1.5 m2, every 5 days for 1.5–2 m2, and every 4 days for BSA >2 m2.Conclusion and Relevance A novel popPK model was developed describing vedolizumab kinetics in haematological patients with refractory GI-GVHD. Body surface area and age were identified as determinants of clearance. Model based dosing may optimise early drug exposure, potentially improving clinical outcomes and response times in this complex patient population.",
  "authors": [
    {
      "affiliations": [
        "Hospital of Salamanca, Hospital Pharmacy, Salamanca"
      ],
      "name": "M López Álvarez"
    },
    {
      "affiliations": [
        "Hospital of Salamanca, Hospital Pharmacy, Salamanca"
      ],
      "name": "N Martín Gutiérrez"
    },
    {
      "affiliations": [
        "Hospital of Salamanca, Hospital Pharmacy, Salamanca"
      ],
      "name": "JG Sánchez Hernández"
    },
    {
      "affiliations": [
        "Hospital of Salamanca, Haematology, Salamanca"
      ],
      "name": "L López Corral"
    },
    {
      "affiliations": [
        "Hospital of Salamanca, Hospital Pharmacy, Salamanca"
      ],
      "name": "C Sánchez Arroyo"
    },
    {
      "affiliations": [
        "Hospital of Salamanca, Hospital Pharmacy, Salamanca"
      ],
      "name": "C Aparicio Carreño"
    },
    {
      "affiliations": [
        "Hospital of Salamanca, Hospital Pharmacy, Salamanca"
      ],
      "name": "MJ Otero López"
    }
  ],
  "title": "NP-007 Population pharmacokinetic model to optimise vedolizumab dosing in haematological patients with refractory gastrointestinal graft-versus-host disease",
  "uid": "9d209ac0-4b15-5a1b-a227-6faf23c404d6"
}