Fixed Dosing Versus Body Size—Based Dosing of Monoclonal Antibodies in Adult Clinical Trials

Journal of Clinical Pharmacology - Tập 49 Số 9 - Trang 1012-1024 - 2009
Diane D. Wang1, Shuzhong Zhang1, Hong Zhao2, Angela Men2, Kourosh Parivar1
1Pfizer Oncology, San Diego, California
2Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research (CDER), Food and Drug Administration (FDA), Silver Spring, Maryland

Tóm tắt

Although without clear scientific rationale, body size—based dosing is often used for administering monoclonal antibodies (mAbs). This simulation study compared the performance of body size—based and fixed dosing in reducing pharmacokinetic (PK) and/or pharmacodynamic (PD) variability in adults for 12 mAbs with published population PK and/or PD models. At the population level, 95th percentile intervals of concentration‐time profiles, distribution, and variability of exposure for 1000 subjects after both dosing approaches were examined. At the individual level, the difference between the exposures of patients with extreme body sizes from the typical exposure following both approaches was compared. The results show that the 2 dosing approaches perform similarly across the mAbs investigated with fixed dosing being better for some mAbs and body size—based dosing being better for the others. Based on this finding, we recommend using fixed dosing in first‐in‐human (FIH) adult studies because it offers other advantages. When sufficient data become available, a full assessment of body size effect on PK/PD should be conducted to determine the optimal dosing approach for phase 3 trials. Other factors that may affect the selection of dosing approach were also discussed. Dosing approach for mAbs in the pediatric population is out of the scope of this study.

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Journal of Clinical Pharmacology

Tập 49 Số 9

1012-1024

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