Letters
Pharmacology
Volume 200 - Issue 2

Pharmacometrics: an underused resource in Australian clinical research

Authors:  Vidya Perera, Michael J Dolton, Andrew J McLachlan, Vaughan J Carr and Richard O Day

Med J Aust 2014; 200 (2): 82-83. || doi: 10.5694/mja13.10663
Published online: 3 February 2014
To the Editor: Pharmacometrics is an emerging field in Australia, with use in a wide range of therapeutic areas including cardiovascular disease, critical patient care, diabetes and paediatrics.1-4 The results of pharmacometric analyses are often referred to in Therapeutic Goods Administration-approved product information; however, for many clinicians, pharmacometrics remains a mysterious area of research. Therefore, we seek to promote the discipline of pharmacometrics in clinical ...
Download PDF (110 KB)
Share: Share on Blue Sky Share on Facebook Share on LinkedIn Share by email

To the Editor: Pharmacometrics is an emerging field in Australia, with use in a wide range of therapeutic areas including cardiovascular disease, critical patient care, diabetes and paediatrics.1-4 The results of pharmacometric analyses are often referred to in Therapeutic Goods Administration-approved product information; however, for many clinicians, pharmacometrics remains a mysterious area of research. Therefore, we seek to promote the discipline of pharmacometrics in clinical practice.

Pharmacometrics has its underpinnings in the principles of clinical pharmacology.5 It has been defined as “the science of developing and applying mathematical and statistical methods to: (a) characterize, understand, and predict a drug’s pharmacokinetic and pharmacodynamic behavior, (b) quantify uncertainty of information about that behavior, and (c) rationalize data-driven decision making in the drug development process and pharmacotherapy”.6

In the United States, pharmacometric analysis is widely applied in drug development and is used by the Food and Drug Administration to determine optimal dosing regimens and first in-human dose selection for clinical trials. Its application can be used to answer important questions such as “what dose will provide therapeutic efficacy?” and “which patients are at greatest risk of adverse drug reactions?”.7

The clinical application of pharmacometrics has been demonstrated by Duong and colleagues.3 Using Monte Carlo simulation, a commonly used pharmacometric tool, they found that metformin, typically contraindicated in patients with renal impairment, can be used in such patients, with appropriate dose adjustments based on stage of renal impairment to avoid toxicity.3 They pooled sparse concentration data and developed a population pharmacokinetic model for metformin. This model then allowed the quantification of different variables (genetics, age, creatinine, total body weight and renal function) on the pharmacokinetic parameters of metformin that affect drug exposure. They performed simulations to identify the dose that did not exceed toxic concentrations for each stage of renal function.

Pharmacometric approaches have also been embraced to individualise treatment with aminoglycoside antibiotics, with dose-prediction software now recommended in Australian guidelines (http://www.tg. org.au/etg_demo/desktop/tgc/abg/7823.htm).

Pharmacometrics holds great promise to truly personalise medicine. Collaboration between clinicians and pharmacometricians could finally remove “hit and miss” approaches to dose selection.

Authors

  • Vidya Perera1
  • Michael J Dolton2
  • Andrew J McLachlan2
  • Vaughan J Carr3
  • Richard O Day3
  • 1. Department of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
  • 2. Faculty of Pharmacy, University of Sydney, Sydney, NSW.
  • 3. University of New South Wales, Sydney, NSW.

Correspondence: vidyaper@buffalo.edu

Competing interests

No relevant disclosures.

References

View this article on Wiley Online Library