Biomarkers of disease activity and other factors as predictors of adalimumab pharmacokinetics in inflammatory bowel disease

Autor: Noemí Rebollo, Fernando Muñoz, Jonás Samuel Pérez-Blanco, José Germán Sánchez-Hernández, Vanessa Prieto, M. V. Calvo
Rok vydání: 2020
Předmět:
musculoskeletal diseases
Adult
Male
medicine.medical_specialty
Injections
Subcutaneous
Population
Anti-Inflammatory Agents
Pharmaceutical Science
02 engineering and technology
030226 pharmacology & pharmacy
Gastroenterology
Inflammatory bowel disease
Models
Biological
03 medical and health sciences
Feces
0302 clinical medicine
Pharmacokinetics
Crohn Disease
Internal medicine
Adalimumab
medicine
Humans
Computer Simulation
skin and connective tissue diseases
education
education.field_of_study
medicine.diagnostic_test
business.industry
Middle Aged
021001 nanoscience & nanotechnology
medicine.disease
Faecal calprotectin
Ulcerative colitis
Therapeutic drug monitoring
Biomarker (medicine)
Colitis
Ulcerative
Female
Drug Monitoring
0210 nano-technology
business
Leukocyte L1 Antigen Complex
Biomarkers
medicine.drug
Zdroj: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 150
ISSN: 1879-0720
Popis: Inflammatory bowel disease (IBD) is commonly treated with adalimumab. The main objective of the study was to develop a population pharmacokinetic model of adalimumab in IBD patients evaluating the potential biomarkers of disease activity and other factors and its implications in adalimumab dosing. A prospective observational study was performed in adult patients diagnosed with Crohn's disease and ulcerative colitis treated with adalimumab and following a proactive therapeutic drug monitoring of serum concentrations. Adalimumab serum concentrations (ASC) were quantified mainly prior the administration using an enzyme-linked immunosorbent assay (ELISA). A population pharmacokinetic model was developed based on 303 ASC data of 104 IBD patients using non-linear mixed effect modelling approach. Sixty-five ASC from 20 additional patients were randomly selected as an external validation group. A one-compartment model with first order absorption and elimination best describe the ASC time course. Body mass index (BMI), faecal calprotectin (FCP), unexplained decline in ASC and the specific administration pen device exhibited significant influence on apparent clearance (p-value < 0.001). FCP was the inflammatory activity biomarker showing the most relevant impact on adalimumab exposure, higher than C-reactive protein and albumin, and may be useful for adalimumab dosing adjustment. The population-based pharmacokinetic model developed adequately characterized adalimumab exposure in IBD patients. The unexplained decline in ASC, FCP, BMI and the specific administration pen device were identified as meaningful variables significantly influencing adalimumab pharmacokinetics.
Databáze: OpenAIRE
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