HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:
Sign In to gain access to subscriptions and/or personal tools.

This Article Full Text Full Text (PDF) 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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Request Reprints Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Miles, D. R. Articles by Boswell, G. W. Search for Related Content PubMed PubMed Citation Articles by Miles, D. R. Articles by Boswell, G. W. Social Bookmarking                         What's this?

Population Pharmacokinetics of Motexafin Gadolinium in Adults With Brain Metastases or Glioblastoma Multiforme

From Pharmacyclics Inc, Sunnyvale, California (Dr Miles, Dr Smith, Dr Phan, Dr Renschler, Dr Boswell); Quintiles Inc, Kansas City, Missouri (Dr Hutcheson); and UCLA Medical Center, Radiation Oncology, Los Angeles, California (Dr Ford).

The purpose of this study was to determine clinical variables affecting motexafin gadolinium (MGd) pharmacokinetics. Motexafin gadolinium (4-5.3 mg/kg/d) was administered intravenously for 2 to 6.5 weeks. Plasma samples from 3 clinical trials were analyzed for MGd using liquid chromatography/mass spectroscopy. The pooled data were analyzed using population pharmacokinetic (POP-PK) methods. The POP-PK model included 243 patients (1575 samples). Clearance (CL) was 14% lower in women, but weight-normalized clearance was only 5% lower in women. Clearance decreased with increasing alkaline phosphatase, increasing age, and decreasing hemoglobin. Administration of phenytoin increased CL by approximately 30%. Central compartment volume (V₁) was 21% lower in women and increased with increasing serum creatinine. For all covariates, except sex and phenytoin, the predicted change in CL or V₁ (5th and 95th percentiles) varied 13% from the population mean CL or V₁ estimate. It was concluded that a 3-compartment, open, POP-PK model predicts small but significant effects of age, sex, alkaline phosphatase, hemoglobin, serum creatinine, and phenytoin on MGd pharmacokinetics.

Key Words: Motexafin gadolinium • population pharmacokinetics • brain metastases • glioblastoma multiforme

Address for reprints: Dale R. Miles, Pharmacyclics Inc, 995 E. Arques Avenue, Sunnyvale, CA 94085.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				K. A. Bradley, I. F. Pollack, J. M. Reid, P. C. Adamson, M. M. Ames, G. Vezina, S. Blaney, P. Ivy, T. Zhou, M. Krailo, et al. Motexafin gadolinium and involved field radiation therapy for intrinsic pontine glioma of childhood: A Children's Oncology Group phase I study Neuro Oncology, October 1, 2008; 10(5): 752 - 758. [Abstract] [Full Text] [PDF]

				G. De Stasio, D. Rajesh, J. M. Ford, M. J. Daniels, R. J. Erhardt, B. H. Frazer, T. Tyliszczak, M. K. Gilles, R. L. Conhaim, S. P. Howard, et al. Motexafin-Gadolinium Taken Up In vitro by at Least 90% of Glioblastoma Cell Nuclei Clin. Cancer Res., January 1, 2006; 12(1): 206 - 213. [Abstract] [Full Text] [PDF]