QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Résumé Extracto Full Text PDF Alert me when this article is cited Alert me if a correction is posted 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 Articles Ahead of Print [Order Reprint] Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ette, E. I Articles by Williams, P. J Search for Related Content PubMed PubMed Citation Articles by Ette, E. I Articles by Williams, P. J

PHARMACOKINETICS

Population Pharmacokinetics II: Estimation Methods

Senior Director of Clinical Pharmacology, Vertex Pharmaceuticals, Inc., Cambridge, MA

Paul J Williams, PharmD MS FCP FCCP

Professor of Pharmacy, Department of Pharmacy Practice, School of Pharmacy, University of the Pacific; Trials by Design, LLC, Stockton, CA

Reprints: Ene I Ette MSc PhD FCP FCCP, Vertex Pharmaceuticals, Inc., 130 Waverly St., Cambridge, MA 02139-4242, fax 617/444-6713, Ene_Ette{at}vpharm.com

OBJECTIVE: To present, compare, and contrast the various approaches to estimating population pharmacokinetic (PPK) models with respect to the mathematical foundation, statistical aspects, software programs for implementation, and underlying assumptions.

DATA SOURCES: Information on PPK was retrieved from a MEDLINE search (1977–August 2004) of literature and a bibliographic review of review articles and books. This information is used in conjunction with experience to explain the various methodologic approaches to PPK.

STUDY SELECTION AND DATA EXTRACTION: All articles indentified from data sources were evaluated and relevant information was included in this review.

DATA SYNTHESIS: Over 80 articles dealing with PPK estimation methods and/or their implementation were identified and reviewed. Sixty-four of these were chosen for their direct relevance to the subject of this article. Different estimation methods ranging from the naïve averaging and naïve pooled approaches through the standard two-stage approach to the nonlinear mixed-effects modeling approaches for estimating PPK are reviewed with their advantages and limitations.

CONCLUSIONS: PPK estimation methods that rely on the characterizing of mixed (fixed and random) effects are known to produce PPK parameter estimates that are less biased than those obtained using the naïve and standard two-stage approaches. The NONMEM software is the most widely used software for the characterization of PPK.

Key Words: estimation, pharmacokinetics, population

Published Online, September 14, 2004. www.theannals.com, DOI 10.1345/aph.1E259

This article has been cited by other articles:

				C. S. Yue, W. Huang, M. Alton, A. N. Maroli, R. W. Waltrip, D. Wright, and M. D. Marco Population Pharmacokinetic and Pharmacodynamic Analysis of Pegloticase in Subjects With Hyperuricemia and Treatment-Failure Gout J. Clin. Pharmacol., June 1, 2008; 48(6): 708 - 718. [Abstract] [Full Text] [PDF]

				K. L. Bigos, R. R. Bies, and B. G. Pollock Population Pharmacokinetics in Geriatric Psychiatry Am J Geriatr Psychiatry, December 1, 2006; 14(12): 993 - 1003. [Abstract] [Full Text] [PDF]

				F. E. Lotrich, R. R. Bies, G. S. Smith, and B. G. Pollock Relevance of assessing drug concentration exposure in pharmacogenetic and imaging studies. J Psychopharmacol, July 1, 2006; 20(4 Suppl): 33 - 40. [Abstract] [PDF]

				E. I Ette, P. J Williams, and J. R Lane Population Pharmacokinetics III: Design, Analysis, and Application of Population Pharmacokinetic Studies Ann. Pharmacother., December 1, 2004; 38(12): 2136 - 2144. [Abstract] [Full Text] [PDF]