Drug dosage individualization based on a random-effects linear lodel

Francisco J. Diaz, Myladis R. Cogollo, Edoardo Spina, Vincenza Santoro, Diego M. Rendon, Jose De Leon

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


This article investigates drug dosage individualization when the patient population can be described with a random-effects linear model of a continuous pharmacokinetic or pharmacodynamic response. Specifically, we show through both decision-theoretic arguments and simulations that a published clinical algorithm may produce better individualized dosages than some traditional methods of therapeutic drug monitoring. Since empirical evidence suggests that the linear model may adequately describe drugs and patient populations, and linear models are easier to handle than the nonlinear models traditionally used in population pharmacokinetics, our results highlight the potential applicability of linear mixed models to dosage computations and personalized medicine.

Original languageEnglish
Pages (from-to)463-484
Number of pages22
JournalJournal of Biopharmaceutical Statistics
Issue number3
StatePublished - May 1 2012

Bibliographical note

Funding Information:
The clozapine study described in this article was conducted at the Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, and IRCCS Centro Neurolesi “Bonino-Pulejo,” Messina, Italy. In 1997, Dr. de Leon lectured once supported by Novartis. In the year since January 11, 2009 he has taken part in a National Institutes of Health (NIH) grant in collaboration with Genomas. He has never been a consultant for a pharmaceutical or pharmacogenetic company. M. R. Cogollo was partially supported by the grant “Apoyo a Estudiantes Sobresalientes de Posgrado” from the Universidad Nacional, Colombia. Dr. Diaz was partially supported by the “Vicedecanatura de Investigación” of the Faculty of Sciences of the Universidad Nacional, Medellin. Dr. Diaz’s involvement in this work lasted 421 years; the first 3 years were at the Universidad Nacional, Medellin, Colombia, and the remaining 121 years at the University of Kansas, Kansas City, KS. In the last year, Dr. Spina has lectured supported by Eli Lilly, Janssen, AstraZeneca, and Bristol-Myers Squibb. Lorraine Maw, MA, helped edit the article.


  • Bayes' theorem
  • Bayesian feedback
  • Clozapine
  • Decision theory
  • Drug dosage individualization
  • Personalized medicine
  • Population pharmacokinetics
  • Random-effects linear models
  • Therapeutic drug monitoring
  • Therapeutic window

ASJC Scopus subject areas

  • Statistics and Probability
  • Pharmacology
  • Pharmacology (medical)


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