Predicting pharmacokinetic profile of therapeutic antibodies after iv injection from only the data after sc injection in cynomolgus monkey

• Published in: Xenobiotica Vol. 47; no. 3; pp. 194 - 201
• Main Authors: Haraya, Kenta, Tachibana, Tatsuhiko, Nezu, Junichi
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 04.03.2017
• Subjects: Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - pharmacokinetics; Antibodies, Monoclonal - therapeutic use; Bioavailability; Biological Availability; FcRn; Humans; Injections, Intravenous; Injections, Subcutaneous; Macaca fascicularis; Models, Biological; PK prediction; therapeutic monoclonal antibody; two-compartment model; FcRn; Bioavailability; PK prediction; therapeutic monoclonal antibody; two-compartment model
• ISSN: 0049-8254; 1366-5928
• DOI: 10.1080/00498254.2016.1174792

1. The number of developed therapeutic monoclonal antibodies (mAbs) has increased in this decade. This study aims to predict their pharmacokinetic profiles after intravenous (iv) injection using only the data taken after subcutaneous (sc) injection in cynomolgus monkey. 2. Two-compartment model parameters, Q, V c and V p , were collected from the published data after iv injection in cynomolgus monkey for 21 mAbs (Group A). Bioavailability after sc injection (F), CL and serum/plasma concentration after iv injection of other published 19 mAbs (Group B) were predicted using the estimated geometric means of Q, V c and V p in Group A and the serum/plasma concentration after sc injection in Group B. 3. F and CL of 18 out of 19 mAbs in Group B were successfully predicted within 30% difference of observed value. Moreover, most of the observed serum/plasma concentrations after iv injection of mAbs in Group B were successfully predicted within 2-fold difference. Our approach suggests that iv injection might not be required to evaluate absorption of mAbs after sc injection in cynomolgus monkey. Therefore, our approach might reduce the time and cost of drug development, reduce the burden on resources, and also contribute to animal welfare.