Evidence map›Paper›PMID 37386339›Full record

ArticleThe AAPS journal2023

Integration of Biorelevant Pediatric Dissolution Methodology into PBPK Modeling to Predict In Vivo Performance and Bioequivalence of Generic Drugs in Pediatric Populations: a Carbamazepine Case Study.

Gopal Pawar, Fang Wu, Liang Zhao, Lanyan Fang, Gilbert J Burckart, Kairui Feng, Youssef M Mousa, Abdullah Al Shoyaib, Marie-Christine Jones, Hannah K Batchelor

Abstract read
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Article in The AAPS journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed.

  1. Review
  2. Article
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  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. IVIVC Revised.Pharmaceutical research · 2024
    Article
  11. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Gopal PawarSchool of Pharmacy, Institute of Clinical Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. G.Pawar@bham.ac.uk.
Fang WuDivision of Quantitative Methods and Modelling, Office of Research and Standard, Office of Generic Drug Products, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, 20993, USA. Fang.Wu@fda.hhs.gov.
Liang ZhaoDivision of Quantitative Methods and Modelling, Office of Research and Standard, Office of Generic Drug Products, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, 20993, USA.
Lanyan FangDivision of Quantitative Methods and Modelling, Office of Research and Standard, Office of Generic Drug Products, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, 20993, USA.
Gilbert J BurckartOffice of Clinical Pharmacology, Office of Translational Science, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, 20993, USA.
Kairui FengDivision of Quantitative Methods and Modelling, Office of Research and Standard, Office of Generic Drug Products, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, 20993, USA.
Youssef M MousaDivision of Quantitative Methods and Modelling, Office of Research and Standard, Office of Generic Drug Products, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, 20993, USA.
Abdullah Al ShoyaibDivision of Quantitative Methods and Modelling, Office of Research and Standard, Office of Generic Drug Products, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, 20993, USA.
Marie-Christine JonesSchool of Pharmacy, Institute of Clinical Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Hannah K BatchelorStrathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow, G4 0RE, UK. Hannah.batchelor@strath.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

This study investigated the impact of gastro-intestinal fluid volume and bile salt (BS) concentration on the dissolution of carbamazepine (CBZ) immediate release (IR) 100 mg tablets and to integrate these in vitro biorelevant dissolution profiles into physiologically based pharmacokinetic modelling (PBPK) in pediatric and adult populations to determine the biopredictive dissolution profile. Dissolution profiles of CBZ IR tablets (100 mg) were generated in 50-900 mL biorelevant adult fasted state simulated gastric and intestinal fluid (Ad-FaSSGF and Ad-FaSSIF), also in three alternative compositions of biorelevant pediatric FaSSGF and FaSSIF medias at 200 mL. This study found that CBZ dissolution was poorly sensitive to changes in the composition of the biorelevant media, where dissimilar dissolution (F2 = 46.2) was only observed when the BS concentration was changed from 3000 to 89 μM (Ad-FaSSIF vs Ped-FaSSIF 50% 14 BS). PBPK modeling demonstrated the most predictive dissolution volume and media composition to forecast the PK was 500 mL of Ad-FaSSGF/Ad-FaSSIF media for adults and 200 mL Ped-FaSSGF/FaSSIF media for pediatrics. A virtual bioequivalence simulation was conducted by using Ad-FaSSGF and/or Ad-FaSSIF 500 mL or Ped-FaSSGF and/or Ped-FaSSIF 200 mL dissolution data for CBZ 100 mg (reference and generic test) IR product. The CBZ PBPK models showed bioequivalence of the product. This study demonstrates that the integration of biorelevant dissolution data can predict the PK profile of a poorly soluble drug in both populations. Further work using more pediatric drug products is needed to verify biorelevant dissolution data to predict the in vivo performance in pediatrics.

Indexed as

BenzodiazepinesDrugs, GenericAdultBile Acids and SaltsCarbamazepineChildHumansSolubilityTherapeutic EquivalencyBenzodiazepinesBile Acids and SaltsCarbamazepineDrugs, Genericcarbamazepine tabletsin vitro dissolutionPBPKpediatric biorelevant dissolution mediavirtual bioequivalence

Identifiers

PMID37386339

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.