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The AAPS Journal

, 21:10 | Cite as

Golimumab Dried Blood Spot Analysis (GOUDA): a Prospective Trial Showing Excellent Correlation with Venepuncture Samples and More Detailed Pharmacokinetic Information

  • Iris Detrez
  • Ganel Schops
  • Jolien Lefrère
  • Sophie Tops
  • Gert Van Assche
  • Séverine Vermeire
  • Wouter Van Moerkercke
  • Marc Ferrante
  • Ann Gils
Research Article
  • 151 Downloads

Abstract

Development of a dried blood spot (DBS) method for golimumab will facilitate sample collection in a study setting and will give a more complete insight in the total drug exposure (area under the curve, AUC). We established a DBS method and assessed its robustness, user-friendliness and clinical usefulness in 10 patients with ulcerative colitis during golimumab induction and maintenance regimens. DBS was obtained through spotting of golimumab spiked in whole citrated blood to a filter paper. Several extraction conditions were evaluated and the selected extraction condition analytically validated. In a clinical setting, DBS and serum samples were taken simultaneously through intensive sampling regimens and a conversion factor was determined. Golimumab concentrations were measured using an in-house-developed ELISA and a CE-marked ELISA kit. User-friendliness was evaluated using a questionnaire. Mucosal healing was evaluated at week 14. A total of 79 matched pairs of serum and DBS sample golimumab concentrations revealed an overall conversion factor of 3.9. DBS golimumab concentrations after conversion correlated strongly with serum golimumab concentrations (ICC = 0.984). During induction, no linear correlation was found between golimumab trough concentration (TC) and AUC (R2 = 0.29). Multiple peaks emerged during drug absorption. Patients who achieved mucosal healing appeared to have less fluctuating TC and a constant AUC over time. Nine out of 10 patients reported DBS sampling as user-friendly. The GOUDA study showed that DBS sampling is a robust and patient-friendly alternative to venous blood collection. DBS sampling may provide better insights into golimumab absorption and exposure. (ClinicalTrials.gov NCT02910375)

KEY WORDS

dried blood spots golimumab immunogenicity pharmacokinetics ulcerative colitis 

Notes

ACKNOWLEDGMENTS

This work was supported by the Fund for Scientific Research Flanders [TBM-T003716N], an investigator-initiated study grant received from Merck and the Flanders Innovation & Entrepreneurship to [ID].

Supplementary material

12248_2018_282_MOESM1_ESM.docx (13 kb)
ESM 1 (DOCX 13 kb)

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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Iris Detrez
    • 1
  • Ganel Schops
    • 2
  • Jolien Lefrère
    • 2
  • Sophie Tops
    • 1
  • Gert Van Assche
    • 2
  • Séverine Vermeire
    • 2
  • Wouter Van Moerkercke
    • 2
    • 3
  • Marc Ferrante
    • 2
  • Ann Gils
    • 1
  1. 1.Department of Pharmaceutical and Pharmacological Sciences, Laboratory for Therapeutic and Diagnostic AntibodiesKU LeuvenLeuvenBelgium
  2. 2.Department of Gastroenterology and Hepatology, Translational Research in Gastrointestinal Disorders, UZ LeuvenKU LeuvenLeuvenBelgium
  3. 3.Department of GastroenterologyAZ GroeningeKortrijkBelgium

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