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Clinical Pharmacokinetics

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01-01-2021 | Pharmacokinetics | Original Research Article

Simple Approach to Accurately Predict Pharmacokinetics of Therapeutic Monoclonal Antibodies after Subcutaneous Injection in Humans

Authors: Kenta Haraya, Tatsuhiko Tachibana

Published in: Clinical Pharmacokinetics | Issue 1/2021

Abstract

Background and objective

The subcutaneous injection of therapeutic monoclonal antibodies is increasingly used in the treatment of several diseases because of its convenience. Thus, a simple and accurate method of predicting the pharmacokinetics of monoclonal antibodies after a subcutaneous injection in humans would be a valuable tool for preclinical/clinical development. In this study, we investigated whether the pharmacokinetics of monoclonal antibodies after a subcutaneous injection in humans can be predicted using only pharmacokinetic data after a subcutaneous injection in cynomolgus monkeys.

Methods

First, we compared the accuracy of three approaches to predict the apparent clearance (CL/F) and apparent volume of distribution (V_d/F) for 15 monoclonal antibodies in humans (1) allometric scaling from cynomolgus monkeys; (2) geometric mean of reported values in humans; (3) estimation from a regression line based on CL/F in humans [only V_d/F]). Then, using the predicted CL/F and V_d/F, and the geometric mean of reported absorption rate constant of mAbs the plasma concentration–time profiles of 13 monoclonal antibodies after subcutaneous injections in humans were simulated.

Results

In a comparison of approaches, the first approach showed the best prediction accuracy for CL/F with an exponent of 0.9 (100% and 73% prediction accuracy within 2- and 1.5-fold of the observed value),and the third approach was the best for V_d/F (100% prediction accuracy within 1.5-fold of the observed value). Next, using the first approach for CL/F and the third approach for V_d/F, we accurately predicted the plasma concentration–time profiles of 13 monoclonal antibodies after subcutaneous injections in humans.

Conclusion

This simple approach can be applied in preclinical and clinical settings to predict the pharmacokinetics of monoclonal antibodies after subcutaneous injections in humans. Further, this approach requires only CL/F after a subcutaneous injection in cynomolgus monkeys, contributing to animal welfare and reducing costs.

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Title: Simple Approach to Accurately Predict Pharmacokinetics of Therapeutic Monoclonal Antibodies after Subcutaneous Injection in Humans
Authors: Kenta Haraya
Tatsuhiko Tachibana
Publication date: 01-01-2021
Publisher: Springer International Publishing
Keyword: Pharmacokinetics
Published in: Clinical Pharmacokinetics / Issue 1/2021
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI: https://doi.org/10.1007/s40262-020-00917-8

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Simple Approach to Accurately Predict Pharmacokinetics of Therapeutic Monoclonal Antibodies after Subcutaneous Injection in Humans

Abstract

Background and objective

Methods

Results

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background and objective

Methods

Results

Conclusion

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