Method Profile
A blood–tissue–lymph PBPK model represents antibody transport, FcRn recycling and α4β7-mediated disposition, with effective target capacity estimated from adult clinical pharmacokinetic data.
Research assessment of disease-related differences in vedolizumab clearance and trough exposure in adults with ulcerative colitis or Crohn’s disease.
Minimal PBPK in Simcyp 22.0, including FcRn recycling and quasi-equilibrium TMDD; Rmax varies by disease-severity group.
Fit and evaluate healthy-adult profiles, adapt Rmax for adult IBD groups, assess Japanese patient profiles and simulate maintenance exposure.
Clinical data
Published healthy-adult and adult-IBD concentration–time profiles, including single doses of 0.2–10 mg/kg.
Model inputs
Literature-derived drug and physiological inputs; target-abundance parameters estimated from group-specific clinical profiles.
Compare simulated mean profiles and exposure ratios with clinical observations. Each scenario uses 10 trials of 10 virtual individuals, giving 100 simulated people.
Healthy-adult development and comparison are followed by severity-specific adult IBD modeling and an external Japanese-population assessment.
Published adult clinical data; 100 virtual individuals per simulation scenario.
Observed mean clinical profiles and exposure measures across the healthy and disease groups.
Healthy-adult Cmax and AUC P/O ranges were 0.81–1.11 and 0.80–1.02; mild-to-moderate UC ranges were 0.88–1.02 and 0.78–0.99; moderate-to-severe UC/CD trough ratios were 0.67–1.49.
A minimal PBPK model represents α4β7 binding alongside antibody distribution and recycling. Fitting an effective target-abundance parameter helped explain exposure differences between healthy adults and people with inflammatory bowel disease.
