Evaluating an easy sampling method using dried blood spots to determine vedolizumab concentrations

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 185; p. 113224
• Main Authors: Bian, Sumin, Van den Berghe, Nathalie, Vandersmissen, Liesbeth, Tops, Sophie, Vermeire, Séverine, Ferrante, Marc, Gils, Ann, Thomas, Debby
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 05.06.2020
• Subjects: Adult; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - analysis; Antibodies, Monoclonal, Humanized - pharmacokinetics; Dried blood spot; Dried Blood Spot Testing - methods; Drug Monitoring - methods; Enzyme-Linked Immunosorbent Assay; Female; Gastrointestinal Agents - administration & dosage; Gastrointestinal Agents - analysis; Gastrointestinal Agents - pharmacokinetics; Humans; Inflammatory bowel diseases; Inflammatory Bowel Diseases - blood; Inflammatory Bowel Diseases - drug therapy; Limit of Detection; Male; Middle Aged; Pharmacokinetics; Therapeutic drug monitoring; Vedolizumab; Therapeutic drug monitoring; Inflammatory bowel diseases; Vedolizumab; Pharmacokinetics; Dried blood spot
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2020.113224

[Display omitted] •A method for vedolizumab concentration measurements in dried blood spots (DBS) was developed.•The method was clinically validated using paired DBS and serum samples from VDZ-treated patients.•Vedolizumab concentrations in DBS extracts strongly correlated with serum concentrations.•Vedolizumab DBS can be used for intensive sampling to gain more insight in its pharmacokinetics. An association between vedolizumab (VDZ) trough concentrations and therapeutic outcome has been observed in patients with inflammatory bowel diseases. VDZ samples are typically collected via venous sampling for therapeutic drug monitoring (TDM), but can alternatively be collected via dried blood spot (DBS) samples, which can be used for intensive sampling to investigate pharmacokinetic profiles. Therefore, we have developed a DBS method for determining VDZ concentrations and validated this method by comparing VDZ measurements in paired DBS and venous patient samples. First, VDZ was spiked in citrated whole blood and spotted on filter paper. After drying, DBS were extracted and VDZ concentrations were determined in the extracts using ELISA. For clinical validation, 41 paired DBS and serum samples were collected from 19 VDZ-treated patients. VDZ concentrations measured in DBS extracts strongly correlated with serum concentrations (Pearson r = 0.978, p < 0.0001). No significant impact of the hematocrit value was observed on the VDZ DBS/serum concentration ratios. Additionally, the VDZ DBS/serum ratio was calculated in nine individual patients, which was, in general, shown to be stable over time. VDZ DBS sampling is a robust method that can be used as an alternative to venous blood collection for TDM of VDZ. VDZ concentrations in DBS highly correlated with VDZ serum concentrations over a broad concentration range, allowing DBS to be used for intensive sampling to gain more insight in VDZ pharmacokinetics.