Title : Population Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics Modeling of Oxypurinol in Hmong Adults with Gout and/or Hyperuricemia
Running title : PK/PD/PGx modeling of oxypurinol
Authors : Ya-Feng Wen, Pharm.D.1, Richard C. Brundage, Pharm.D., Ph.D.1, Youssef M. Roman, Pharm.D., Ph.D.2, Kathleen A. Culhane-Pera, M.D., M.A.3, Robert J. Straka, Pharm.D., FCCP1
Affiliations :
  1. Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA
  2. Department of Pharmacotherapy & Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA
  3. Minnesota Community Care, St. Paul, MN 55107, USA
Corresponding Author :
Robert J. Straka Experimental and Clinical Pharmacology University of Minnesota College of Pharmacy 308 Harvard St SE, Minneapolis, MN 55455 Email: strak001@umn.edu ORCiD iD: 0000-0002-9541-7823
The authors confirm that the Principal Investigator for this paper is Robert J. Straka and that he had direct clinical responsibility for patients.
Data availability : Raw data is not available to the public due to lack of patient consent for data sharing. NONMEM control files for pharmacokinetics and pharmacodynamics modeling and R script for allopurinol dose simulation are available in the supplemental text 1-4.
Funding : This work was supported by the University of Minnesota, Office of Community Engagement of the Clinical and Translational Science Institute for its funding via 2014 Collaborative Pilot Grants No. 22556 and National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR000114. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Conflict of interest disclosure : All listed authors declare no conflicts of interest.
Ethics approval : This study was approved by the Human Research Protection Program at the University of Minnesota IRB (# 1408M53223).
Patient consent : Consent was obtained for all the study participants prior to any study related activities.
ClinicalTrials.gov Identifier : NCT02371421
Key words : allopurinol, gout, population pharmacokinetics, NONMEM, pharmacometrics
Word count : 4044
Table count : 3
Figure count : 3
What is already known about this subject
What this study adds
Genetic variants in SLC22A12 were associated with oxypurinol clearance and variants in PDZK1 were associated with urate-lowering effect of oxypurinol.
The allopurinol maintenance dose to achieve target serum urate level depends on patients’ body mass, renal function, and genetic variants in SLC22A12 and PDZK1.