Evidence map›Paper›PMID 42198901›Full record

ArticleClinical pharmacology and therapeutics2026

Characterization of Lysosomal Hydrolases and Transporters and Their Age-Dependent Variability: Relevance to Drug Metabolism and Transport of Small Molecule and Biologic Drugs.

Darshak Gadara, Dilip Kumar Singh, Sandhya Subash, Guihua Yue, Deepak Ahire, Chris Bohl, Maciej Czerwinski, Stephanie Helmstetter, Scott Heyward, Robert S Jones and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical pharmacology and therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

21 authors.

Darshak GadaraDivision of Translational and Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Dilip Kumar SinghDivision of Translational and Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Sandhya SubashDivision of Translational and Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Guihua YueDepartment of Pharmaceutical Sciences, Washington State University, Spokane, WA, USA.
Deepak AhireDrug Metabolism, Gilead Sciences Inc., Foster City, CA, USA.
Chris BohlBioIVT Inc., Baltimore, MD, USA.
Maciej CzerwinskiBioIVT Inc., Baltimore, MD, USA.
Stephanie HelmstetterBioIVT Inc., Baltimore, MD, USA.
Scott HeywardBioIVT Inc., Baltimore, MD, USA.ORCID https://orcid.org/0000-0001-7805-3522
Robert S JonesDepartment of Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, CA, USA.
Cyrus KhojastehDepartment of Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, CA, USA.ORCID https://orcid.org/0000-0002-8385-9288
Ryota KikuchiQuantitative, Translational & ADME Sciences Department, AbbVie, North Chicago, IL, USA.
Priyanka KulkarniDrug Metabolism and Pharmacokinetics, Takeda Development Center Americas, Inc., Cambridge, MA, USA.
Bin MaDepartment of Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, CA, USA.ORCID https://orcid.org/0000-0002-7549-2658
Bernard MurrayDrug Metabolism, Gilead Sciences Inc., Foster City, CA, USA.
Chris SeibBioIVT Inc., Baltimore, MD, USA.
Bill SmithTerminal Phase Consulting LLC, Colorado Springs, CO, USA.
David M StresserQuantitative, Translational & ADME Sciences Department, AbbVie, North Chicago, IL, USA.
Mitchell E TaubDrug Metabolism and Pharmacokinetics, Clinical Pharmacology and Safety, Boehringer Ingelheim, Inc., Ridgefield, CT, USA.
Ting WangDrug Metabolism and Pharmacokinetics, Clinical Pharmacology and Safety, Boehringer Ingelheim, Inc., Ridgefield, CT, USA.
Bhagwat PrasadDivision of Translational and Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.ORCID https://orcid.org/0000-0002-9090-0912

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Lysosomes play a key role in the accumulation, catabolism, and transport of endogenous and exogenous metabolites and proteins and are involved in drug metabolism and prodrug activation. However, the protein abundance and interindividual variability of lysosomal drug-metabolizing enzymes and transporters (DMETs) remain underexplored. In this study, we performed a global proteomics analysis of the enriched human liver lysosomal fraction to characterize and annotate lysosomal proteins and compared these results with the proteomics data of hepatocyte homogenates and the liver microsomal fraction. We annotated and quantified 66 hydrolases and 41 membrane transporters in the lysosomal fractions. These included proteins involved in prodrug activation, transport, and metabolism or functioning as drug targets. After confirming the identity of lysosomal proteins, we investigated age-dependent changes in the abundance of these proteins in human hepatocytes (n = 58) across various age groups, ranging from neonatal (0-12 days) to adulthood (>18 years). We observed age-specific variations in the expression of key hydrolases (CTSA, CTSL, NAGLU, PLD3, and GALNS) and transporters (ATP6V1B2, ATP6V1C1, TMEM63A, and SLC39A14). Together, these findings highlight the lysosomal localization of proteins involved in drug disposition and their dynamic developmental changes, providing critical insights for refining physiologically based pharmacokinetic (PBPK) models to support precision dosing and improve therapeutic outcomes in pediatric populations.

Identifiers

PMID42198901
PMCPMC13339043

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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.