Evidence map›Paper›PMID 37231199›Full record

ReviewThe AAPS journal2023

Impact of Organ Impairment on the Pharmacokinetics of Therapeutic Peptides and Proteins.

Elimika Pfuma Fletcher, Martina Sahre, Yuen Yi Hon, Anand Balakrishnan, Lin Zhou, Qin Sun, Jie Wang, Kimberly Maxfield, Raajan Naik, Shiew Mei Huang and 1 more

Abstract readReview
PubMed Publisher
In one paragraph

Review 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 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
4.6field-weighted citation impact, top 6% of its field
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

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
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

11 authors at 2 institutions in 1 country.

Elimika Pfuma FletcherOffice of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA.
Martina SahreOffice of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA.
Yuen Yi HonOffice of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine, Office of New Drug, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Anand BalakrishnanOffice of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA.
Lin ZhouOffice of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA.
Qin SunOffice of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA.
Jie WangOffice of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA.
Kimberly MaxfieldOffice of Therapeutic Biologics and Biosimilars, Office of New Drug, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Raajan NaikOffice of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA.
Shiew Mei HuangOffice of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA.
Yow-Ming C WangOffice of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA. yowming.wang@fda.hhs.gov.
United States Food and Drug Administration · USCenter for Drug Evaluation and Research · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The kidneys and liver are major organs involved in eliminating small-molecule drugs from the body. Characterization of the effects of renal impairment (RI) and hepatic impairment (HI) on pharmacokinetics (PK) have informed dosing in patients with these organ impairments. However, the knowledge about the impact of organ impairment on therapeutic peptides and proteins is still evolving. In this study, we reviewed how often therapeutic peptides and proteins were assessed for the effect of RI and HI on PK, the findings, and the resulting labeling recommendations. RI effects were reported in labeling for 30 (57%) peptides and 98 (39%) proteins and HI effects for 20 (38%) peptides and 55 (22%) proteins. Dose adjustments were recommended for RI in 11 of the 30 (37%) peptides and 10 of the 98 (10%) proteins and for HI in 7 of the 20 (35%) peptides and 3 of the 55 (5%) proteins. Additional actionable labeling includes risk mitigation strategies; for example, some product labels have recommended avoid use or monitor toxicities in patients with HI. Over time, there is an increasing structural diversity of therapeutic peptides and proteins, including the use of non-natural amino acids and conjugation technologies, which suggests a potential need for reassessing the need to evaluate the effect of RI and HI. Herein, we discuss scientific considerations for weighing the risk of PK alteration due to RI or HI for peptide and protein products. We briefly discuss other organs that may affect the PK of peptides and proteins administered via other delivery routes.

Indexed as

KidneyRenal InsufficiencyHumansPeptidesPharmaceutical PreparationsProteinsPeptidesPharmaceutical PreparationsProteinshepatic impairmentpeptidespharmacokineticsproteinsrenal impairment

Identifiers

PMID37231199
OpenAlexW4378190093

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.