Academic Journal
PKGPT: Expert-Orchestrated Recursive LLM Agent for Automated NONMEM PopPK Modeling with Human Benchmarking.
| Τίτλος: | PKGPT: Expert-Orchestrated Recursive LLM Agent for Automated NONMEM PopPK Modeling with Human Benchmarking. |
|---|---|
| Συγγραφείς: | Kwack, Hoyoung, Kong, Hyunseung, Lim, Jiwoo, Zhang, Byoung-Tak, Hahn, Jongsung, Chang, Min Jung |
| Πηγή: | Pharmaceutics; Apr2026, Vol. 18 Issue 4, p501, 20p |
| Θεματικοί όροι: | Pharmacokinetics, Language models |
| Εταιρία/Οντότητα: | Google Inc. |
| Περίληψη: | Background/Objectives: Population pharmacokinetic (PopPK) modeling in NONMEM requires iterative, expertise-dependent workflows. Naïve zero-shot prompting of general-purpose large language models (LLMs) typically produces NONMEM code that fails to execute. This study introduces PKGPT, a recursive agentic LLM system designed to automate NONMEM-based PopPK model development and benchmarks its performance against human expert models. Methods: PKGPT, powered by Google's Gemini 3.0 Flash, embeds pharmacometrics expertise into phase-specific expert-agent prompts orchestrated across five sequential phases: base model establishment, structural diagnostics, overfitting reduction, random-effects optimization, and covariate analysis. The system recursively executes NONMEM, parses outputs, and iteratively refines control streams. PKGPT was evaluated on three public datasets (warfarin, theophylline, and tobramycin) and benchmarked against independently developed human expert models. Results: PKGPT consistently produced executable, converging NONMEM models across all three datasets. In warfarin, both PKGPT and the human expert selected a one-compartment oral structure (ADVAN2), but the expert achieved a lower OFV (294.41 vs. 484.43) via covariate scaling. In theophylline, PKGPT produced parameter estimates close to the expert solution (Ka = 1.59 vs. 1.46 h−1; CL = 0.0399 vs. 0.0404 L/h/kg). In tobramycin, PKGPT correctly identified a two-compartment structure but produced physiologically implausible peripheral volume estimates (V2 = 149 L vs. expert's 13.2 L). Across datasets, PKGPT did not identify clinically established covariates, and run-to-run reproducibility was variable. Conclusions: PKGPT substantially improves the robustness and usability of LLM-generated NONMEM code compared with naïve zero-shot prompting, accelerating model drafting and iterative refinement, but physiological plausibility and clinical interpretability still require a human-in-the-loop oversight. [ABSTRACT FROM AUTHOR] |
| Copyright of Pharmaceutics is the property of MDPI and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Βάση Δεδομένων: | Biomedical Index |
| FullText | Text: Availability: 0 CustomLinks: – Url: https://resolver.ebsco.com/c/fiv2js/result?sid=EBSCO:edm&genre=article&issn=19994923&ISBN=&volume=18&issue=4&date=20260401&spage=501&pages=501-520&title=Pharmaceutics&atitle=PKGPT%3A%20Expert-Orchestrated%20Recursive%20LLM%20Agent%20for%20Automated%20NONMEM%20PopPK%20Modeling%20with%20Human%20Benchmarking.&aulast=Kwack%2C%20Hoyoung&id=DOI:10.3390/pharmaceutics18040501 Name: Full Text Finder (for New FTF UI) (ns324271) Category: fullText Text: Full Text Finder MouseOverText: Full Text Finder |
|---|---|
| Header | DbId: edm DbLabel: Biomedical Index An: 193439461 RelevancyScore: 1041 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 1041.07458496094 |
| IllustrationInfo | |
| Items | – Name: Title Label: Title Group: Ti Data: PKGPT: Expert-Orchestrated Recursive LLM Agent for Automated NONMEM PopPK Modeling with Human Benchmarking. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Kwack%2C+Hoyoung%22">Kwack, Hoyoung</searchLink><br /><searchLink fieldCode="AR" term="%22Kong%2C+Hyunseung%22">Kong, Hyunseung</searchLink><br /><searchLink fieldCode="AR" term="%22Lim%2C+Jiwoo%22">Lim, Jiwoo</searchLink><br /><searchLink fieldCode="AR" term="%22Zhang%2C+Byoung-Tak%22">Zhang, Byoung-Tak</searchLink><br /><searchLink fieldCode="AR" term="%22Hahn%2C+Jongsung%22">Hahn, Jongsung</searchLink><br /><searchLink fieldCode="AR" term="%22Chang%2C+Min+Jung%22">Chang, Min Jung</searchLink> – Name: TitleSource Label: Source Group: Src Data: Pharmaceutics; Apr2026, Vol. 18 Issue 4, p501, 20p – Name: Subject Label: Subject Terms Group: Su Data: <searchLink fieldCode="DE" term="%22Pharmacokinetics%22">Pharmacokinetics</searchLink><br /><searchLink fieldCode="DE" term="%22Language+models%22">Language models</searchLink> – Name: SubjectCompany Label: Company/Entity Group: Su Data: <searchLink fieldCode="CO" term="%22Google+Inc%2E%22">Google Inc.</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Background/Objectives: Population pharmacokinetic (PopPK) modeling in NONMEM requires iterative, expertise-dependent workflows. Naïve zero-shot prompting of general-purpose large language models (LLMs) typically produces NONMEM code that fails to execute. This study introduces PKGPT, a recursive agentic LLM system designed to automate NONMEM-based PopPK model development and benchmarks its performance against human expert models. Methods: PKGPT, powered by Google's Gemini 3.0 Flash, embeds pharmacometrics expertise into phase-specific expert-agent prompts orchestrated across five sequential phases: base model establishment, structural diagnostics, overfitting reduction, random-effects optimization, and covariate analysis. The system recursively executes NONMEM, parses outputs, and iteratively refines control streams. PKGPT was evaluated on three public datasets (warfarin, theophylline, and tobramycin) and benchmarked against independently developed human expert models. Results: PKGPT consistently produced executable, converging NONMEM models across all three datasets. In warfarin, both PKGPT and the human expert selected a one-compartment oral structure (ADVAN2), but the expert achieved a lower OFV (294.41 vs. 484.43) via covariate scaling. In theophylline, PKGPT produced parameter estimates close to the expert solution (Ka = 1.59 vs. 1.46 h<superscript>−1</superscript>; CL = 0.0399 vs. 0.0404 L/h/kg). In tobramycin, PKGPT correctly identified a two-compartment structure but produced physiologically implausible peripheral volume estimates (V2 = 149 L vs. expert's 13.2 L). Across datasets, PKGPT did not identify clinically established covariates, and run-to-run reproducibility was variable. Conclusions: PKGPT substantially improves the robustness and usability of LLM-generated NONMEM code compared with naïve zero-shot prompting, accelerating model drafting and iterative refinement, but physiological plausibility and clinical interpretability still require a human-in-the-loop oversight. [ABSTRACT FROM AUTHOR] – Name: Abstract Label: Group: Ab Data: <i>Copyright of Pharmaceutics is the property of MDPI and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
| PLink | https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edm&AN=193439461 |
| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.3390/pharmaceutics18040501 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 20 StartPage: 501 Subjects: – SubjectFull: Google Inc. Type: general – SubjectFull: Pharmacokinetics Type: general – SubjectFull: Language models Type: general Titles: – TitleFull: PKGPT: Expert-Orchestrated Recursive LLM Agent for Automated NONMEM PopPK Modeling with Human Benchmarking. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Kwack, Hoyoung – PersonEntity: Name: NameFull: Kong, Hyunseung – PersonEntity: Name: NameFull: Lim, Jiwoo – PersonEntity: Name: NameFull: Zhang, Byoung-Tak – PersonEntity: Name: NameFull: Hahn, Jongsung – PersonEntity: Name: NameFull: Chang, Min Jung IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 04 Text: Apr2026 Type: published Y: 2026 Identifiers: – Type: issn-print Value: 19994923 Numbering: – Type: volume Value: 18 – Type: issue Value: 4 Titles: – TitleFull: Pharmaceutics Type: main |
| ResultId | 1 |