title: Population pharmacokinetics of infliximab in patients with inflammatory bowel disease: potential implications for dosing in clinical practice.
abstract: BACKGROUND
  Infliximab (IFX) is effective in the treatment of inflammatory bowel diseases (IBD). Currently, IFX is administered at fixed doses and intervals; however, costs are high and optimisation is necessary. Several publications indicate that IFX should be dosed on trough levels ≥3.0 mg/L. For optimising IFX dosing, the use of a pharmacokinetic model is important. Population pharmacokinetics of IFX have been described earlier; however, these models were not used for dose optimising.
  
  
  OBJECTIVE
  To develop a pharmacokinetic model for IFX in IBD patients that can be used for dose-optimisation of IFX and to predict serum trough levels in this population.
  
  
  METHODS
  An observational retrospective study was performed in 42 IFX-treated IBD patients. Serum samples were drawn before infusion at T = 0, 2, 6, 14, 22 and 54 weeks and analysed for IFX and antibodies against IFX (ATI). Relevant covariates were recorded and a population pharmacokinetic model was developed.
  
  
  RESULTS
  Individual plots created using the final model showed good correspondence between observed and model predicted values. Serum levels were influenced by ATI, disease activity, sex and albumin. Our results show that in patients without ATI target trough levels ≥3.0 mg/L can be achieved by increasing dosing intervals from 8 to 12 weeks combined with a dose increase. This results in a reduction of 33% in concomitant costs.
  
  
  CONCLUSIONS
  In IBD patients without ATI, trough level dosing based on longer intervals can reduce IFX therapy-related visits to the hospital with one-third. Trough level based dose intensification should always be justified by disease activity parameters.
authors.affiliation: Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: D J
authors.initials: DJ
authors.lastname: Buurman
authors.affiliation: Department of Clinical Pharmacy and Pharmacology Groningen, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: J M
authors.initials: JM
authors.lastname: Maurer
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, School of Pharmacy, University of California San Francisco, San Francisco, CA, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Keizer
authors.affiliation: Department of Clinical Pharmacy and Pharmacology Groningen, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.|Section Pharmacotherapy and Pharmaceutical Care, Department of Pharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: J G W
authors.initials: JG
authors.lastname: Kosterink
authors.affiliation: Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Dijkstra
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D000069285:Infliximab / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009010:Monte Carlo Method; D012189:Retrospective Studies; D012709:Serum Albumin; D012720:Severity of Illness Index; D012737:Sex Factors
chemical_list: D005765:Gastrointestinal Agents; D012709:Serum Albumin; D000069285:Infliximab