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This Article Full Text Full Text (PDF) All Versions of this Article: 0091270009337512v1 49/9/1012    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Request Reprints Google Scholar Articles by Wang, D. D. Articles by Parivar, K. PubMed PubMed Citation Articles by Wang, D. D. Articles by Parivar, K. Social Bookmarking                         What's this?

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

From Pfizer Oncology, San Diego, California (Dr Wang, Zhang, Parivar); and the Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research (CDER), Food and Drug Administration (FDA), Silver Spring, Maryland (Zhao, Men).

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.

Key Words: Fixed dosing • body size–based dosing • body weight • body surface area • biologics • monoclonal antibodies • population pharmacokinetics • pharmacodynamics

Address for reprints: Diane Wang, PhD, 10646 Science Center Drive, San Diego, CA 92121; e-mail: diane.wang{at}pfizer.com.

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