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4CPS-126 A population pharmacokinetic model of adalimumab in a cohort of paediatric patients with inflammatory bowel disease: a preliminary analysis
  1. M Miarons Font1,
  2. JG Sánchez Hernandez2,
  3. JS Pérez Blanco3,
  4. S Clemente Bautista1,
  5. N Rebollo Diaz2,
  6. O Segarra Cantón4,
  7. MJ Cabañas Poy1,
  8. R Torres Peral5,
  9. MQ Gorgas1,
  10. MJ Otero2
  1. 1Hospital Universitario Vall D’hebron, Pharmacy Department, Barcelona, Spain
  2. 2Complejo Asistencial Universitario De Salamanca, Pharmacy Department, Salamanca, Spain
  3. 3University of Salamanca, Department of Pharmaceutical Sciences, Salamanca, Spain
  4. 4Hospital Universitario Vall D’hebron, Paediatric Gastroenterology Unit, Barcelona, Spain
  5. 5Complejo Asistencial Universitario De Salamanca, Paediatric Gastroenterology Unit, Salamanca, Spain


Background and importance Therapeutic drug monitoring is useful to optimise adalimumab therapy in patients with inflammatory bowel disease (IBD).

Aim and objectives The objective of this study was to perform a preliminary pharmacokinetic (PK) model of adalimumab to evaluate covariates potentially responsible for the PK variability in paediatric patients with IBD.

Material and methods A 3 year retrospective multicentre study was performed including children and adolescent (≤ 18 years) diagnosed with IBD and treated with adalimumab. Demographic and clinical data were collected, including serum albumin, C reactive protein and faecal calprotectin. Pre-dose serum samples were carried out before administration. Adalimumab concentrations and anti-adalimumab antibodies (AAA) were determined by ELISA. The model was developed in NONMEM V.7.4 by approximating the non-linear mixed effects models. The first order conditional estimation method with interaction (FOCEI) was used for model building. Concentrations below the lower limit of quantification (LLOQ) were set to LLOQ/2. Body weight (WGT) was included in the PK parameters following an allometric relationship.

Results Twenty-three paediatric patients (10 women) were included, 3 were diagnosed with ulcerative colitis and 20 with Crohn disease. Median age (range) was 14.0 (5–18) years and weight 55.9 (20.4–80) kg. A total of 75 concentrations (2< LLOQ) were determined, with a medium concentration of 10.72 (0.1–24.7) µg/mL. Median (range) serum albumin level was 4.0 (2.8–5.0) g/dL. Only one patient developed AAA. Population PK model (PopPK): a one compartment with first order absorption and elimination described adequately the serum adalimumab concentration–time data. The absorption rate constant was fixed (Ka=0.008/hour) according to Sharma et al. Among the clinical variables analysed, only albumin was significant on the apparent clearance (CL/F). The final PopPK model in the absence of AAA was as defined as: V/F=11.30×(WGT/56 kg) and CL/F (L/day)=0.42×(albumin/4 g/dL)-2.32 × (WGT/56 kg)0.75. Covariate analysis reduced the interindividual variability associated with CL (IIVCL) from 34.1% to 21.3%. Proportional residual error estimated was 28.4%.

Conclusion and relevance Adalimumab PK in paediatric patients with IBD was best described by a one compartment model with first order absorption and elimination. WGT was included in the PK parameters following an allometric relationship. Albumin showed statistically significant differences on adalimumab CL/F, explaining 62.5% of its variability.

References and/or acknowledgements 1. Sharma S, et al. Inflamm Bowel Dis 2015;21:783–792.

No conflict of interest.

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