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Fixed Dosing Versus Body Size—Based Dosing of Monoclonal Antibodies in Adult Clinical Trials
Author(s) -
Wang Diane D.,
Zhang Shuzhong,
Zhao Hong,
Men Angela Y.,
Parivar Kourosh
Publication year - 2009
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270009337512
Subject(s) - dosing , pharmacokinetics , percentile , medicine , population , pharmacodynamics , pharmacology , statistics , mathematics , environmental health
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.