Application of blood microsampling in cynomolgus monkey and demonstration of equivalent monoclonal antibody PK parameters compared to conventional sampling
| Autor: | Dean Messing, Lisa Dyleski, Sarah J Crowell, Boris Gorovits, Zhiping You, Sarah Murphy, Alison Joyce, Meghan Gomes, Jennifer Cargill, Ying Wang |
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| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.drug_class Drug Evaluation Preclinical Pharmaceutical Science 02 engineering and technology Monoclonal antibody 030226 pharmacology & pharmacy 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Toxicity Tests medicine Animals Pharmacology (medical) Sampling (medicine) Whole blood Pharmacology Blood Specimen Collection Chromatography Chemistry Ligand binding assay Organic Chemistry Antibodies Monoclonal PK Parameters 021001 nanoscience & nanotechnology Serum samples Macaca fascicularis Models Animal Molecular Medicine Feasibility Studies Administration Intravenous Sample collection 0210 nano-technology Biotechnology |
| Zdroj: | Pharmaceutical research. 38(5) |
| ISSN: | 1573-904X |
| Popis: | The purpose of this study was to evaluate the suitability of whole blood microsampling procedures in non-human primate (NHP) to support toxicokinetic assessments of biotherapeutics in non-human primates. A one-month single dose intravenous pharmacokinetic (PK) study was performed in male cynomolgus monkeys with a human IgG1 control monoclonal antibody (mAb) as a surrogate monoclonal antibody biotherapeutic. In this study, both serum samples (conventional sample collection) and microsampling samples were collected. Microsampling samples were collected from two sites on cynomolgus monkey, with each site using two different devices for the whole blood collection. The drug concentrations from all sample types were determined using a quantitative ligand binding assay (LBA). The PK parameters obtained from microsampling samples and serum samples were examined using a standard PK analysis method. The comparability of key PK parameters from both sample types were analyzed statistically. Similar profiles of drug concentrations versus timepoints from all sampling procedures were observed. The correlations of PK concentration data obtained from serum and microsampling samples were ≥ 0.97 using Brand Alman Plot analysis. The key PK parameters obtained from microsampling samples were comparable to those obtained from serum samples (the % differences of mean PK parameters obtained from both sample types were within ±25%). This study confirmed that PK parameters obtained from samples using microsampling were comparable to that of serum samples in cynomolgus monkeys. Therefore, the microsampling procedure described can be used as a substitute for conventional sampling procedure to support PK/TK studies of biotherapeutics in non-clinical product developments. |
| Databáze: | OpenAIRE |
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