Whilst the reproducibility of models in the area of systems biology and quantitative systems pharmacology has been the focus of attention lately, the concept of ‘reusability’ is not addressed. With the advent of the ‘Model Master File’ dominating some regulatory discussions on pharmaceutical applications of physiologically‐based pharmacokinetic (PBPK) models, reusability becomes a vital aspect of confidence in their use. Herein, we define ‘reusability’ specifically in the context of PBPK models and investigate the influence of open versus non‐open source‐code (NOSC) nature of the software on the extent of ‘reusability’. Original articles (n = 145) that were associated with the development of novel PBPK models were identified as source models and citations to these reports, which involved further PBPK model development, were explored (n > 1800) for reuse cases of the source PBPK model whether in full or partial form. The nature of source‐code was a major determinant of external reusability for PBPK models (>50% of the NOSC models as opposed <25% of open source‐code [OSC]). Full reusability of the models was not common and mostly involved internal reuse of the OSC model (by the group who had previously developed the original model). The results were stratified by the software utilised (various), organisations involved (academia, industry, regulatory), and type of reusability (full vs. partial). The clear link between external reuse of models and NOSC PBPK software might stem from many elements related to quality and trust that require further investigation, and challenges the unfounded notion that OSC models are associated with higher uptake for reuse.

PBPK applications published in the literature support a greater adoption of nonopen source-code (NOSC) software as opposed to open source-code (OSC) alternatives. However, a significant number of PBPK modelers are still using OSC software, understanding the rationale for the use of this modality is important and may help those embarking on PBPK modeling. No previous analysis of PBPK modeling trends has included the rationale of the modeler. An in-depth analysis of PBPK applications of OSC software is warranted to determine the true impact of OSC software on the rise of PBPK. Publications focusing on PBPK modeling applications, which used OSC software, were identified by systematically searching the scientific literature for original articles. A total of 171 articles were extracted from the narrowed subset. The rise in the use of OSC software for PBPK applications was greater than the general discipline of pharmacokinetics (9 vs. 4), but less than the overall growth of the PBPK area (9 vs. 43). Our report demonstrates conclusively that the surge in PBPK usage is primarily attributable to the availability and implementations of NOSC software. Modelers preferred not to share the reasons for their selection of certain modeling software and no 'explicit' rationale was given to support the use of OSC analysed by this study. As the preference for NOSC versus OSC software tools in the PBPK area continues to be divided, initiatives to add the rationale in using one form over another to every future PBPK modeling report will be a welcomed and informative addition.