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Human radiolabeled mass balance studies supporting the FDA approval of new drugs
Open accessAbstract
Human radiolabeled mass balance studies are an important component of the clinical pharmacology programs supporting the development of new investigational drugs. These studies allow for understanding of the absorption, distribution, metabolism, and excretion of the parent drug and metabolite(s) in the human body. Understanding the drug's disposition as well as metabolite profiling and abundance via mass balance studies can help inform the overall drug development program. A survey of the US Food and Drug Administration (FDA)-approved new drug applications (NDAs) indicated that about 66% of the drugs had relied on findings from the mass balance studies to help understand the pharmacokinetic characteristics of the drug and to inform the overall drug development program. When such studies were not available in the original NDA, adequate justifications were routinely provided. Of the 104 mass balance studies included in this survey, most of the studies were conducted in healthy volunteers (90%) who were mostly men (>86%). The studies had at least six evaluable participants (66%) and were performed using the final route(s) of administration (98%). Eighty-five percent of the studies utilized a dose within the pharmacokinetic linearity range with 54% of the studies using a dose the same as the approved dose. Nearly all studies were performed as a single-dose (97%) study using a fit-for-purpose radiolabeled formulation. In this analysis, we summarized the current practices for conducting mass balance studies and highlighted the importance of conducting appropriately designed human radiolabeled mass balance studies and the challenges associated with inadequately designed or untimely studies.
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Mass balance studies typically include around five healthy male volunteers receiving a single dose of the investigational drug.
“typically including around five healthy male volunteers receiving a single dose of the investigational drug [20].”
From Pharmacometabolomics Study of Sulfamethoxazole and Trimethoprim in Kidney Transplant Recipients: Real-World Metabolism and Urinary Excretion (2025) · cites this paper as [20]
The Study Population section says mass balance studies are mostly conducted in healthy male volunteers, and the Investigational Drug Route, Dose, and Formulation section reports that 97% were single-dose studies. The sample-size detail differs: the Study Population section reports a typical sample size of six, with six also the recommended minimum, rather than around five. (LLM, conf=0.87)
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Metadata
- Authors
- Ramamoorthy, A., Bende, G., Chow, E. C. Y., Dimova, H., Hartman, N., Jean, D., Pahwa, S., Ren, Y., Shukla, C., Yang, Y., Doddapaneni, S., & Danielsen, Z. Y.
- Affiliations
- United States Food and Drug Administration (US)
- Corresponding author
- Doddapaneni, Suresh
- Danielsen, Zhixia Yan
- ORCID
- Venue
- Clinical and Translational Science
- Publisher
- Wiley
- Published
- 2022-09-23
- Volume
- 15
- Issue
- 11
- Pages
- 2567-2575
- ISSN
- 1752-8054 (ISSN-L)
- 1752-8062
- PMC
- PMC9652429
- OpenAlex
- W4294783759
- Cited by
- 40
- References
- 12
- Citations by year
- 2026: 14 · 2025: 16 · 2024: 7 · 2023: 1 · 2022: 2
- FWCI
- 5.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Clinical and Translational Science (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Keywords
- drug metabolism, drug disposition, pharmacokinetics, drug metabolites, clinical pharmacology, healthy volunteers, research design, drug development, ADME
- MeSH terms
- Data Collection, Pharmaceutical Preparations, Female, Humans, Male, Pharmacology, Clinical, United States, United States Food and Drug Administration, Drugs, Investigational, Drug Approval
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