The pharmacokinetics of infliximab induction therapy in patients with moderate to severe ulcerative colitis

  • J.F. B
  • D. V
  • G.-J. W
 et al. 
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Abstract

Background: The mechanism behind primary non-response to infliximab (IFX) in patients with Ulcerative Colitis (UC) is not fully understood. Although insufficient serum concentrations of IFX have been suggested as a cause of lack of response associated with a high inflammatory load (and hence large quantities of TNF to be neutralized), the early pharmacokinetics (PK) of IFX during induction therapy have been poorly studied. We studied the PK of IFX induction treatment related to inflammatory load and response in patients with moderate and severe UC. Methods: In this multicenter prospective observational study anti- TNF Naive patients with moderate-to-severe Ulcerative Colitis (Endoscopic Mayo 2/3) starting on IFX were included after baseline endoscopy. Serum IFX concentrations, antibodies to IFX and fecal samples (IFX concentration) were collected at 10 serial time points during the first 6 weeks of induction therapy. Response was defined by endoscopic improvement at week 6-8. PK was analysed by nonlinear mixed-effects modelling and described using a 2-compartiment PK model. Results: Fifteen UC patients were included. All but one patient received IFX according to the regular induction regime of 5mg/kg at week 0,2,6 and 7/15 with concomitant thiopurines. 8/15 patients had no endoscopic improvement. Typical values and corresponding inter-patient variability (IPV) for clearance, intercompartimental clearance, central and peripheral volume of distribution were 0.44 L/day (IPV 26%), 0.52 L/day, 3.5 L (IPV 20%) and 3.2 L (IPV 130%). Median 'trough' level before third infusion (week 6) was 2.5 ug/ml for endoscopic non-responders versus 8.2 ug/ml for responders (P=0.03). Serum IFX of

Author-supplied keywords

  • *gastrointestinal disease
  • *human
  • *infliximab
  • *patient
  • *pharmacokinetics
  • *therapy
  • *ulcerative colitis
  • antibody
  • blood level
  • endoscopy
  • infusion
  • mercaptopurine
  • model
  • observational study
  • serum

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Authors

  • Brandse J.F.

  • Van Der Kleij D.

  • Wolbink G.-J.

  • Rigter I.M.

  • Baars P.A.

  • Lowenberg M.

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