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

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 (Vd/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 Vd/F]). Then, using the predicted CL/F and Vd/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 Vd/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 Vd/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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Correspondence to Kenta Haraya.

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This work was fully supported by Chugai Pharmaceutical Co. Ltd.

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Kenta Haraya and Tatsuhiko Tachibana are employees of Chugai Pharmaceutical Co. Ltd. and declare no potential conflicts of interest that might be relevant to the content of this article.

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All pharmacokinetic data is available in reference and all software is commercially available.

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K.H. and T.T. contributed to the study concept, data analysis and preparation of manuscript.

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Haraya, K., Tachibana, T. Simple Approach to Accurately Predict Pharmacokinetics of Therapeutic Monoclonal Antibodies after Subcutaneous Injection in Humans. Clin Pharmacokinet 60, 111–120 (2021). https://doi.org/10.1007/s40262-020-00917-8

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