NDLI: Rationale for Fixed Dosing of Pertuzumab in Cancer Patients Based on Population Pharmacokinetic Analysis

Content Provider	Springer Nature Link
Author	Ng, Chee M. Lum, Bert L. Gimenez, Veronica Kelsey, Steve Allison, David
Copyright Year	2006
Abstract	Our objectives were to develop the population pharmacokinetic (PK) for pertuzumab and examine the variability of steady-state trough serum concentrations (C$_{SS,trough}$) and exposure after fixed, body-weight-based, or body-surface area (BSA)-based dosing methods in cancer patients.Pertuzumab was administered by IV infusion (every 3 weeks) either as a weight-based dose (0.5–15 mg/kg) or a fixed dose (420 or 1050 mg). Data from three clinical studies, comprising 153 patients and 1458 concentration-time points, were pooled for this analysis using NONMEM.A linear two-compartment model best described the data. Body weight and BSA were significant covariates affecting clearance (CL) and distribution volume (Vc), respectively. However, weight and BSA only explained small percentage of interpatient variability for CL and Vc, respectively. Simulation results indicated that PK profiles were very similar after the three dosing methods. Compared to fixed dosing, weight- and BSA-based dosing only reduced the population variability of C$_{SS,trough}$ moderately.A population PK model was developed for pertuzumab, the first monoclonal IgG1 antibody in a new class of agents known as HER dimerization inhibitors. In addition, our analyses demonstrate the feasibility of administering pertuzumab using a fixed dose in women with ovarian and breast cancers.
Starting Page	1275
Ending Page	1284
Page Count	10
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	23
Issue Number	6
e-ISSN	1573904X
Language	English
Publisher	Springer-Verlag
Publisher Date	2006-05-26
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	cancer fixed dosing human epidermal growth factor receptors monoclonal antibody population pharmacokinetics Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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