Volume 52, Issue 1 p. 18-28

Fixed Dosing Versus Body Size—Based Dosing of Therapeutic Peptides and Proteins in Adults

Dr Shuzhong Zhang PhD

Dr Shuzhong Zhang PhD

Pfizer Oncology, San Diego, California

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Ms Rong Shi MS

Ms Rong Shi MS

Department of Pharmaceutics, University of Florida, Gainesville

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Dr Chunze Li PhD

Dr Chunze Li PhD

Pfizer Oncology, San Diego, California

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Dr Kourosh Parivar MS

Dr Kourosh Parivar MS

Pfizer Oncology, San Diego, California

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Dr Diane D. Wang PhD

Corresponding Author

Dr Diane D. Wang PhD

Pfizer Oncology, San Diego, California

Address for correspondence: Dione D. Wang, PhD, Pfizer Oncology, 10646 Science Center Dr, San Diego, CA 92121; e-mail: [email protected].Search for more papers by this author
First published: 07 March 2013
Citations: 31

Abstract

Therapeutic biologics are often administered based on body size. A previous study has found that fixed dosing performs similarly to body size—based dosing in reducing intersubject variability in drug exposure across the mAbs studied. This study extended this evaluation to other therapeutic proteins and peptides. Eighteen therapeutic proteins and peptides with published population pharmacokinetic (PK) and/or pharmacodynamic (PD) models were selected for dosing approach evaluation. The relationships between body size and drug exposure (and PD end point when available) were evaluated, and simulation studies were conducted to compare the performance of the 2 dosing approaches. The results showed that fixed dosing performed better for 12 of 18 selected biologics in terms of reducing intersubject variability in exposure at both population and individual levels, whereas body size—based dosing performed better for the other 6 molecules. This result is consistent with the findings for mAbs. Therefore, fixed dosing is recommended for first-in-human studies of proteins and peptides along with mAbs. The final dosing approach for phase 3 studies should be determined based on a full assessment of body size effect on PK/PD when data are available and the therapeutic window of the drug.