Estimation of Clearance and Bioavailability of Therapeutic Monoclonal Antibodies from Only Subcutaneous Injection Data in Humans Based on Comprehensive Analysis of Clinical Data.

摘要: Introduction Theoretically, the separate estimation of clearance (CL) and bioavailability (F) requires both intravenous extravascular injection data. This study investigated whether CL subcutaneous F therapeutic monoclonal antibodies (mAbs) in humans can be separately estimated from data only. Methods First, geometric mean linear pharmacokinetic parameters (CL, intercompartmental [Q], volume distribution central compartment [Vc], peripheral [Vp]) after for mAbs that have been reported public sources was 103 with pharmacokinetics 44 nonlinear pharmacokinetics. Next, we 25 plasma/serum mAb concentration-time profiles by fixing Q, Vc, Vp based on Moreover, profile simulated using Vp. Results There were no significant differences among subclasses (immunoglobulin [Ig] G1, 2, 4) or linearity (derivation pharmacokinetics). Using only data, successfully 23/25 (92%) all (100%) within 1.5-fold observed value. overall, largely consistent (90.8% values). Conclusions approach does not require to estimate therefore accelerate clinical development mAbs.