Component

First-pass metabolism during and after absorption

First-pass metabolism during and after absorption. Species, exposure and limitations are retained in each linked claim.

4 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. Tritiated dihydrocapsaicin and unlabelled capsaicin were readily absorbed from the gastrointestinal tract but were almost completely metabolized before reaching the general circulation, with less than 5% of total extracted radioactivity consisting of unchanged dihydrocapsaicin in trunk blood and brain 15 minutes after gastrointestinal application, against approximately 50% unchanged 3 minutes after intravenous or 90 minutes after subcutaneous application.

    First-pass metabolism during and after absorption → Unchanged dihydrocapsaicin reaching trunk blood and brain source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    biomarker_context Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/dihydrocapsaicin-research/2280802.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "92a4527b69cd4c342da3d0aed850597ef4491122baf20b6a681e43ab0a8e2dd1", "start_char": 0, "end_char": 1280, "text_sha256": "92a4527b69cd4c342da3d0aed850597ef4491122baf20b6a681e43ab0a8e2dd1"}
    experimental_model
    Intragastric, intravenous and subcutaneous administration of tritiated dihydrocapsaicin in anaesthetised rats with tissue extraction
    exposure
    Tritiated dihydrocapsaicin and unlabelled capsaicin given intragastrically, intravenously or subcutaneously
    limitations
    The comparison across routes is the point, and it is the reason every hypothermia study in this collection injects the drug rather than feeding it. Anaesthetised rats, and identification is chromatographic.
    nutrient_topic
    Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin
    organism
    Rat
    plain_language
    Swallowed, almost none of it reaches the brain intact; injected, about half does.
    primary_references
    [dhc-p2280802] Absorption and metabolism of capsaicinoids following intragastric administration in rats. (1990). https://pubmed.ncbi.nlm.nih.gov/2280802/ DOI: 10.1007/bf00169449
    tissue_or_cell_type
    Portal blood, trunk blood, brain and liver
    trigger_kind
    biomarker_context Imported condition classification; unverified.

    Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 504–515

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Intragastric, intravenous and subcutaneous administration of tritiated dihydrocapsaicin in anaesthetised rats with tissue extraction · source_derived_draft · unverified_draft

    ### dhc-first-pass-destroys-it Tritiated dihydrocapsaicin and unlabelled capsaicin were readily absorbed from the gastrointestinal tract but were almost completely metabolized before reaching the general circulation, with less than 5% of total extracted radioactivity consisting of unchanged dihydrocapsaicin in trunk blood and brain 15 minutes after gastrointestinal application, against approximately 50% unchanged 3 minutes after intravenous or 90 minutes after subcutaneous application. Condition category: biomarker_context nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: Swallowed, almost none of it reaches the brain intact; injected, about half does. organism: Rat tissue_or_cell_type: Portal blood, trunk blood, brain and liver experimental_model: Intragastric, intravenous and subcutaneous administration of tritiated dihydrocapsaicin in anaesthetised rats with tissue extraction limitations: The comparison across routes is the point, and it is the reason every hypothermia study in this collection injects the drug rather than feeding it. Anaesthetised rats, and identification is chromatographic. exposure: Tritiated dihydrocapsaicin and unlabelled capsaicin given intragastrically, intravenously or subcutaneously evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/2280802.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "92a4527b69cd4c342da3d0aed850597ef4491122baf20b6a681e43ab0a8e2dd1", "start_char": 0, "end_char": 1280, "text_sha256": "92a4527b69cd4c342da3d0aed850597ef4491122baf20b6a681e43ab0a8e2dd1"} [dhc-p2280802] Absorption and metabolism of capsaicinoids following intragastric administration in rats. (1990). https://pubmed.ncbi.nlm.nih.gov/2280802/ DOI: 10.1007/bf00169449
    Complete structured claim and evidence

What acts on it

  1. Dihydrocapsaicin was metabolized when incubated in vitro with liver tissue but not with brain tissue, a certain degree of biotransformation already took place in the intestinal lumen, there appears to be a saturable absorption and degradation process in the gastrointestinal tract and very effective metabolism in the liver, and the metabolic products did not show capsaicin-like biological activity.

    Dihydrocapsaicin → First-pass metabolism during and after absorption source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/dihydrocapsaicin-research/2280802.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "92a4527b69cd4c342da3d0aed850597ef4491122baf20b6a681e43ab0a8e2dd1", "start_char": 0, "end_char": 1280, "text_sha256": "92a4527b69cd4c342da3d0aed850597ef4491122baf20b6a681e43ab0a8e2dd1"}
    experimental_model
    Intragastric, intravenous and subcutaneous administration of tritiated dihydrocapsaicin in anaesthetised rats with tissue extraction
    exposure
    Tritiated dihydrocapsaicin and unlabelled capsaicin given intragastrically, intravenously or subcutaneously
    limitations
    The comparison across routes is the point, and it is the reason every hypothermia study in this collection injects the drug rather than feeding it. Anaesthetised rats, and identification is chromatographic.
    nutrient_topic
    Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin
    organism
    Rat
    plain_language
    The liver breaks it down and the brain does not, and what the liver makes is inert.
    primary_references
    [dhc-p2280802] Absorption and metabolism of capsaicinoids following intragastric administration in rats. (1990). https://pubmed.ncbi.nlm.nih.gov/2280802/ DOI: 10.1007/bf00169449
    tissue_or_cell_type
    Portal blood, trunk blood, brain and liver

    Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 517–528

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Intragastric, intravenous and subcutaneous administration of tritiated dihydrocapsaicin in anaesthetised rats with tissue extraction · source_derived_draft · unverified_draft

    ### dhc-liver-not-brain Dihydrocapsaicin was metabolized when incubated in vitro with liver tissue but not with brain tissue, a certain degree of biotransformation already took place in the intestinal lumen, there appears to be a saturable absorption and degradation process in the gastrointestinal tract and very effective metabolism in the liver, and the metabolic products did not show capsaicin-like biological activity. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: The liver breaks it down and the brain does not, and what the liver makes is inert. organism: Rat tissue_or_cell_type: Portal blood, trunk blood, brain and liver experimental_model: Intragastric, intravenous and subcutaneous administration of tritiated dihydrocapsaicin in anaesthetised rats with tissue extraction limitations: The comparison across routes is the point, and it is the reason every hypothermia study in this collection injects the drug rather than feeding it. Anaesthetised rats, and identification is chromatographic. exposure: Tritiated dihydrocapsaicin and unlabelled capsaicin given intragastrically, intravenously or subcutaneously evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/2280802.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "92a4527b69cd4c342da3d0aed850597ef4491122baf20b6a681e43ab0a8e2dd1", "start_char": 0, "end_char": 1280, "text_sha256": "92a4527b69cd4c342da3d0aed850597ef4491122baf20b6a681e43ab0a8e2dd1"} [dhc-p2280802] Absorption and metabolism of capsaicinoids following intragastric administration in rats. (1990). https://pubmed.ncbi.nlm.nih.gov/2280802/ DOI: 10.1007/bf00169449
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. The structure of the glucuronide metabolites of capsaicin and dihydrocapsaicin that appeared in the perfusate during 90 minutes of luminal perfusion of a standardised Capsicum extract was identified by mass spectrometry.

    Dihydrocapsaicin → Glucuronide conjugates of capsaicin and dihydrocapsaicin source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/dihydrocapsaicin-research/25462121.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "667a4d33ee4b6423efe4532d0138ba6eb68a08fcc41b33ff5d04f442ad6f6177", "start_char": 0, "end_char": 1576, "text_sha256": "667a4d33ee4b6423efe4532d0138ba6eb68a08fcc41b33ff5d04f442ad6f6177"}
    experimental_model
    Validated reverse-phase HPLC with fluorescence detection applied to rat small intestine luminal perfusion
    exposure
    Standardised Capsicum extract at 30 micrograms per millilitre perfused luminally for 90 minutes
    limitations
    Primarily a method development paper. The substantive finding recorded here is the identification of glucuronide conjugates of both compounds in the perfusate by mass spectrometry.
    nutrient_topic
    Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin
    organism
    Rat
    plain_language
    The gut also attaches a sugar group to both compounds while they are being absorbed.
    primary_references
    [dhc-p25462121] A validated HPLC-FLD method for analysis of intestinal absorption and metabolism of capsaicin and dihydrocapsaicin in the rat. (2015). https://pubmed.ncbi.nlm.nih.gov/25462121/ DOI: 10.1016/j.jpba.2014.10.007
    tissue_or_cell_type
    Small intestine lumen

    Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 556–567

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Validated reverse-phase HPLC with fluorescence detection applied to rat small intestine luminal perfusion · source_derived_draft · unverified_draft

    ### dhc-glucuronidation-in-gut The structure of the glucuronide metabolites of capsaicin and dihydrocapsaicin that appeared in the perfusate during 90 minutes of luminal perfusion of a standardised Capsicum extract was identified by mass spectrometry. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: The gut also attaches a sugar group to both compounds while they are being absorbed. organism: Rat tissue_or_cell_type: Small intestine lumen experimental_model: Validated reverse-phase HPLC with fluorescence detection applied to rat small intestine luminal perfusion limitations: Primarily a method development paper. The substantive finding recorded here is the identification of glucuronide conjugates of both compounds in the perfusate by mass spectrometry. exposure: Standardised Capsicum extract at 30 micrograms per millilitre perfused luminally for 90 minutes evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/25462121.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "667a4d33ee4b6423efe4532d0138ba6eb68a08fcc41b33ff5d04f442ad6f6177", "start_char": 0, "end_char": 1576, "text_sha256": "667a4d33ee4b6423efe4532d0138ba6eb68a08fcc41b33ff5d04f442ad6f6177"} [dhc-p25462121] A validated HPLC-FLD method for analysis of intestinal absorption and metabolism of capsaicin and dihydrocapsaicin in the rat. (2015). https://pubmed.ncbi.nlm.nih.gov/25462121/ DOI: 10.1016/j.jpba.2014.10.007
    Complete structured claim and evidence

  2. Tritiated dihydrocapsaicin was mainly absorbed via the portal system and not by a mesenteric lymphangial one, and the radioactivity in portal blood was composed of 85% dihydrocapsaicin and 15% of its metabolite 8-methyl nonanoic acid bound to the albumin fraction, with dihydrocapsaicin-hydrolysing enzyme activity found in jejunal tissue, indicating a partial first-pass effect during absorption.

    Dihydrocapsaicin → 8-methyl nonanoic acid, the methyl-branched medium-chain fatty acid released from dihydrocapsaicin source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/dihydrocapsaicin-research/6710495.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a0a9a5cb2178f2b266fffe5efbd9580a0a1b5c03dd86b4bfe92b105194eb1f9b", "start_char": 0, "end_char": 1416, "text_sha256": "a0a9a5cb2178f2b266fffe5efbd9580a0a1b5c03dd86b4bfe92b105194eb1f9b"}
    experimental_model
    In vivo and in situ gastrointestinal absorption studies in rats with tritiated dihydrocapsaicin
    exposure
    Capsaicin and dihydrocapsaicin administered into stomach, jejunum and ileum, with 2,4-dinitrophenol and sodium cyanide as metabolic inhibitors
    limitations
    Establishes both the route and the first metabolite by direct measurement in portal blood. A 1984 rat study using tritium label rather than mass spectrometry.
    nutrient_topic
    Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin
    organism
    Rat
    plain_language
    The gut wall snips the molecule in two, and one of the pieces is a small fatty acid that travels on in the blood.
    primary_references
    [dhc-p6710495] Gastrointestinal absorption and metabolism of capsaicin and dihydrocapsaicin in rats. (1984). https://pubmed.ncbi.nlm.nih.gov/6710495/ DOI: 10.1016/0041-008x(84)90121-2
    tissue_or_cell_type
    Stomach, jejunum, ileum and portal blood

    Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 491–502

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · In vivo and in situ gastrointestinal absorption studies in rats with tritiated dihydrocapsaicin · source_derived_draft · unverified_draft

    ### dhc-releases-8-mna Tritiated dihydrocapsaicin was mainly absorbed via the portal system and not by a mesenteric lymphangial one, and the radioactivity in portal blood was composed of 85% dihydrocapsaicin and 15% of its metabolite 8-methyl nonanoic acid bound to the albumin fraction, with dihydrocapsaicin-hydrolysing enzyme activity found in jejunal tissue, indicating a partial first-pass effect during absorption. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: The gut wall snips the molecule in two, and one of the pieces is a small fatty acid that travels on in the blood. organism: Rat tissue_or_cell_type: Stomach, jejunum, ileum and portal blood experimental_model: In vivo and in situ gastrointestinal absorption studies in rats with tritiated dihydrocapsaicin limitations: Establishes both the route and the first metabolite by direct measurement in portal blood. A 1984 rat study using tritium label rather than mass spectrometry. exposure: Capsaicin and dihydrocapsaicin administered into stomach, jejunum and ileum, with 2,4-dinitrophenol and sodium cyanide as metabolic inhibitors evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/6710495.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a0a9a5cb2178f2b266fffe5efbd9580a0a1b5c03dd86b4bfe92b105194eb1f9b", "start_char": 0, "end_char": 1416, "text_sha256": "a0a9a5cb2178f2b266fffe5efbd9580a0a1b5c03dd86b4bfe92b105194eb1f9b"} [dhc-p6710495] Gastrointestinal absorption and metabolism of capsaicin and dihydrocapsaicin in rats. (1984). https://pubmed.ncbi.nlm.nih.gov/6710495/ DOI: 10.1016/0041-008x(84)90121-2
    Complete structured claim and evidence

In the sources

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