Nutrient chapter

Tadalafil

Tadalafil. A long-acting competitive inhibitor of phosphodiesterase type 5, with a half-maximal inhibitory concentration of 5 nanomolar and high selectivity for PDE5 over PDE1 to PDE4 and over PDE6; the cis-(6R,12aR) piperazinedione enantiomer carries the potency reported in the discovery series. Like sildenafil it preserves cyclic GMP rather than producing it, and PDE5 carries the principal cyclic GMP hydrolysing activity in human corpus cavernosum, where the downstream relaxation requires cyclic GMP-dependent protein kinase I. What distinguishes it from sildenafil in this ledger is measured rather than asserted: 85-fold greater selectivity against the retinal PDE6, and a mean plasma half-life of 17.5 hours with 5th and 95th percentiles of 11.5 and 29.6 hours. The longer half-life is also the shape of the nitrate interaction, which persisted at 4, 8 and 24 hours and was no longer detectable at 48, 72 and 96 hours. Three endpoints are recorded in three conditions: a 2.3 point improvement in the International Prostate Symptom Score at 5 mg once daily, a 33 metre placebo-corrected increase in six-minute walk distance in pulmonary arterial hypertension where only the 40 mg dose met the prespecified significance level, and the structure of the human PDE5 catalytic domain solved with this drug bound. Its target is recorded as an entity distinct from the homologous retinal PDE6, with no family link joining them, because the selectivity ratio between them is what the comparison above measures. Species, exposure and limitations are retained in each linked claim.

10 recorded mechanisms · 0 availability situations · 1 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

What the sources say this nutrient does, one relationship at a time. Plain wording comes first; the technical statement follows.

  1. Tadalafil is a highly potent PDE5 inhibitor with a half-maximal inhibitory concentration of 5 nanomolar and high selectivity for PDE5 over PDE1 to PDE4 and PDE6.

    Tadalafil → Phosphodiesterase 5 family source_derived_draftungraded
    Experimental context and source evidence
    duration
    Not applicable
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    experimental_model
    Isolated phosphodiesterase enzyme assays during medicinal-chemistry optimisation
    exposure
    Tadalafil, compound GF196960, the cis-(6R,12aR) enantiomer of the piperazinedione series
    limitations
    High diastereospecificity was observed in this series, so potency belongs to the named enantiomer and not to the racemate; selectivity was assessed against PDE1 to PDE4 and PDE6 in this report and not across all twelve families.
    organism
    Isolated phosphodiesterase enzyme assays during medicinal-chemistry optimisation
    plain_language
    Tadalafil is a highly potent PDE5 inhibitor with a half-maximal inhibitory concentration of 5 nanomolar and high selectivity for PDE5 over PDE1 to PDE4 and PDE6.
    primary_references
    The discovery of tadalafil: a novel and highly selective PDE5 inhibitor. 2. (2003). https://pubmed.ncbi.nlm.nih.gov/14521415/ DOI: 10.1021/jm0300577
    route
    In vitro
    tissue
    Phosphodiesterase inhibition across isoenzymes

    Tadalafil: PDE5 occupancy, the cGMP route and three measured endpoints (2026-09-22) · lines 13–22

    Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata. Two references carry an unresolvable erratum and are recorded as corrected. Study-specific doses, effect sizes and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

    ## tadalafil-inhibits-pde5 Tadalafil is a highly potent PDE5 inhibitor with a half-maximal inhibitory concentration of 5 nanomolar and high selectivity for PDE5 over PDE1 to PDE4 and PDE6. Model/species: Isolated phosphodiesterase enzyme assays during medicinal-chemistry optimisation Tissue/system: Phosphodiesterase inhibition across isoenzymes Exposure: Tadalafil, compound GF196960, the cis-(6R,12aR) enantiomer of the piperazinedione series Route: In vitro Duration: Not applicable Limits: High diastereospecificity was observed in this series, so potency belongs to the named enantiomer and not to the racemate; selectivity was assessed against PDE1 to PDE4 and PDE6 in this report and not across all twelve families. Primary reference: The discovery of tadalafil: a novel and highly selective PDE5 inhibitor. 2. (2003). https://pubmed.ncbi.nlm.nih.gov/14521415/ DOI: 10.1021/jm0300577 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

  2. Tadalafil showed 85-fold greater selectivity against PDE6 than sildenafil.

    Tadalafil → Phosphodiesterase 6 family source_derived_draftungraded
    Experimental context and source evidence
    duration
    Not applicable
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    experimental_model
    Isolated phosphodiesterase enzyme assays
    exposure
    Tadalafil compared with sildenafil
    limitations
    A ratio measured in enzyme assays; PDE6 is the retinal phototransduction phosphodiesterase, and this comparison does not by itself establish a difference in visual effects in people.
    organism
    Isolated phosphodiesterase enzyme assays
    plain_language
    Tadalafil showed 85-fold greater selectivity against PDE6 than sildenafil.
    primary_references
    The discovery of tadalafil: a novel and highly selective PDE5 inhibitor. 2. (2003). https://pubmed.ncbi.nlm.nih.gov/14521415/ DOI: 10.1021/jm0300577
    route
    In vitro
    tissue
    Selectivity ratio between PDE5 and PDE6

    Tadalafil: PDE5 occupancy, the cGMP route and three measured endpoints (2026-09-22) · lines 24–33

    Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata. Two references carry an unresolvable erratum and are recorded as corrected. Study-specific doses, effect sizes and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

    ## tadalafil-pde6-selectivity-versus-sildenafil Tadalafil showed 85-fold greater selectivity against PDE6 than sildenafil. Model/species: Isolated phosphodiesterase enzyme assays Tissue/system: Selectivity ratio between PDE5 and PDE6 Exposure: Tadalafil compared with sildenafil Route: In vitro Duration: Not applicable Limits: A ratio measured in enzyme assays; PDE6 is the retinal phototransduction phosphodiesterase, and this comparison does not by itself establish a difference in visual effects in people. Primary reference: The discovery of tadalafil: a novel and highly selective PDE5 inhibitor. 2. (2003). https://pubmed.ncbi.nlm.nih.gov/14521415/ DOI: 10.1021/jm0300577 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

  3. Three-dimensional structures of the catalytic domain of human PDE5, residues 537 to 860, were determined in complex with sildenafil, tadalafil and vardenafil.

    Tadalafil → Phosphodiesterase 5 family source_derived_draftungraded
    Experimental context and source evidence
    duration
    Not applicable
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    experimental_model
    Human PDE5 catalytic domain
    exposure
    Each of the three drug molecules complexed with the enzyme
    limitations
    The catalytic domain alone was crystallised, not the full-length regulated enzyme, so the structures do not describe the allosteric cGMP-binding GAF domains.
    organism
    Human PDE5 catalytic domain
    plain_language
    Three-dimensional structures of the catalytic domain of human PDE5, residues 537 to 860, were determined in complex with sildenafil, tadalafil and vardenafil.
    primary_references
    Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules. (2003). https://pubmed.ncbi.nlm.nih.gov/12955149/ DOI: 10.1038/nature01914
    route
    Structural
    tissue
    Inhibitor binding at the catalytic site

    Tadalafil: PDE5 occupancy, the cGMP route and three measured endpoints (2026-09-22) · lines 35–44

    Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata. Two references carry an unresolvable erratum and are recorded as corrected. Study-specific doses, effect sizes and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

    ## pde5-binding-site-resolved-with-tadalafil Three-dimensional structures of the catalytic domain of human PDE5, residues 537 to 860, were determined in complex with sildenafil, tadalafil and vardenafil. Model/species: Human PDE5 catalytic domain Tissue/system: Inhibitor binding at the catalytic site Exposure: Each of the three drug molecules complexed with the enzyme Route: Structural Duration: Not applicable Limits: The catalytic domain alone was crystallised, not the full-length regulated enzyme, so the structures do not describe the allosteric cGMP-binding GAF domains. Primary reference: Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules. (2003). https://pubmed.ncbi.nlm.nih.gov/12955149/ DOI: 10.1038/nature01914 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

  4. cGMP-specific PDE5 carries out the principal cGMP-hydrolysing activity in human corpus cavernosum tissue.

    Phosphodiesterase 5 family → Cyclic guanosine monophosphate source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    experimental_model
    Human corpus cavernosum tissue, as stated in a structural report
    exposure
    Not applicable
    limitations
    Stated as established background in this structural paper rather than measured in it; twelve PDE gene families exist and others are present in the same tissue.
    organism
    Human corpus cavernosum tissue, as stated in a structural report
    plain_language
    cGMP-specific PDE5 carries out the principal cGMP-hydrolysing activity in human corpus cavernosum tissue.
    primary_references
    Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules. (2003). https://pubmed.ncbi.nlm.nih.gov/12955149/ DOI: 10.1038/nature01914
    route
    Not applicable
    tissue
    Cyclic nucleotide degradation

    Tadalafil: PDE5 occupancy, the cGMP route and three measured endpoints (2026-09-22) · lines 46–54

    Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata. Two references carry an unresolvable erratum and are recorded as corrected. Study-specific doses, effect sizes and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

    ## pde5-hydrolyses-cgmp-in-corpus-cavernosum cGMP-specific PDE5 carries out the principal cGMP-hydrolysing activity in human corpus cavernosum tissue. Model/species: Human corpus cavernosum tissue, as stated in a structural report Tissue/system: Cyclic nucleotide degradation Exposure: Not applicable Route: Not applicable Limits: Stated as established background in this structural paper rather than measured in it; twelve PDE gene families exist and others are present in the same tissue. Primary reference: Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules. (2003). https://pubmed.ncbi.nlm.nih.gov/12955149/ DOI: 10.1038/nature01914 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

  5. Corpora cavernosa from mice lacking cGMP-dependent kinase I failed to relax when the nitric oxide and cGMP signalling cascade was activated.

    cGMP-dependent protein kinase I → Corpus cavernosum smooth muscle relaxation source_derived_draftungraded
    Experimental context and source evidence
    duration
    Acute
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    experimental_model
    cGMP-dependent kinase I null mice compared with normal mice
    exposure
    Activation of the NO/cGMP cascade
    limitations
    A whole-body knockout rather than tissue-specific deletion; the mice also had a very low ability to reproduce, while their sperm were normal and could fertilise eggs.
    organism
    cGMP-dependent kinase I null mice compared with normal mice
    plain_language
    Corpora cavernosa from mice lacking cGMP-dependent kinase I failed to relax when the nitric oxide and cGMP signalling cascade was activated.
    primary_references
    Erectile dysfunction in cyclic GMP-dependent kinase I-deficient mice. (2000). https://pubmed.ncbi.nlm.nih.gov/10688876/ DOI: 10.1073/pnas.030419997
    route
    Isolated tissue
    tissue
    Corpus cavernosum smooth muscle relaxation

    Tadalafil: PDE5 occupancy, the cGMP route and three measured endpoints (2026-09-22) · lines 56–65

    Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata. Two references carry an unresolvable erratum and are recorded as corrected. Study-specific doses, effect sizes and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

    ## cgmp-dependent-kinase-i-carries-the-relaxation Corpora cavernosa from mice lacking cGMP-dependent kinase I failed to relax when the nitric oxide and cGMP signalling cascade was activated. Model/species: cGMP-dependent kinase I null mice compared with normal mice Tissue/system: Corpus cavernosum smooth muscle relaxation Exposure: Activation of the NO/cGMP cascade Route: Isolated tissue Duration: Acute Limits: A whole-body knockout rather than tissue-specific deletion; the mice also had a very low ability to reproduce, while their sperm were normal and could fertilise eggs. Primary reference: Erectile dysfunction in cyclic GMP-dependent kinase I-deficient mice. (2000). https://pubmed.ncbi.nlm.nih.gov/10688876/ DOI: 10.1073/pnas.030419997 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

  6. Raising cyclic AMP with forskolin produced similar relaxation in normal and cGMP-dependent kinase I null corpus cavernosum.

    cGMP-dependent protein kinase I → Corpus cavernosum smooth muscle relaxation source_derived_draftungraded
    Experimental context and source evidence
    duration
    Acute
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    experimental_model
    cGMP-dependent kinase I null mice compared with normal mice
    exposure
    Forskolin
    limitations
    Shows an intact parallel cAMP route in isolated tissue; the authors conclude cAMP signalling cannot compensate for the absent cGMP cascade in vivo, which is an inference from the reproductive phenotype rather than a separate measurement.
    organism
    cGMP-dependent kinase I null mice compared with normal mice
    plain_language
    Raising cyclic AMP with forskolin produced similar relaxation in normal and cGMP-dependent kinase I null corpus cavernosum.
    primary_references
    Erectile dysfunction in cyclic GMP-dependent kinase I-deficient mice. (2000). https://pubmed.ncbi.nlm.nih.gov/10688876/ DOI: 10.1073/pnas.030419997
    route
    Isolated tissue
    tissue
    Corpus cavernosum smooth muscle relaxation

    Tadalafil: PDE5 occupancy, the cGMP route and three measured endpoints (2026-09-22) · lines 67–76

    Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata. Two references carry an unresolvable erratum and are recorded as corrected. Study-specific doses, effect sizes and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

    ## cyclic-amp-does-not-substitute-for-the-cgmp-route Raising cyclic AMP with forskolin produced similar relaxation in normal and cGMP-dependent kinase I null corpus cavernosum. Model/species: cGMP-dependent kinase I null mice compared with normal mice Tissue/system: Corpus cavernosum smooth muscle relaxation Exposure: Forskolin Route: Isolated tissue Duration: Acute Limits: Shows an intact parallel cAMP route in isolated tissue; the authors conclude cAMP signalling cannot compensate for the absent cGMP cascade in vivo, which is an inference from the reproductive phenotype rather than a separate measurement. Primary reference: Erectile dysfunction in cyclic GMP-dependent kinase I-deficient mice. (2000). https://pubmed.ncbi.nlm.nih.gov/10688876/ DOI: 10.1073/pnas.030419997 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

  7. Tadalafil plasma concentrations declined nearly monoexponentially with a mean half-life of 17.5 hours, with 5th and 95th percentiles of 11.5 and 29.6 hours.

    Tadalafil → Plasma tadalafil exposure source_derived_draftungraded
    Experimental context and source evidence
    duration
    Single dose and 10 days
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    experimental_model
    237 healthy subjects across 13 clinical pharmacology studies, with a separate multiple-dose study
    exposure
    Single 2.5 to 20 mg doses, and 10 or 20 mg once daily for 10 days
    limitations
    Healthy subjects only. No clinically meaningful effect of body mass index, age, gender or smoking was identified, and food had negligible effect on bioavailability.
    organism
    237 healthy subjects across 13 clinical pharmacology studies, with a separate multiple-dose study
    plain_language
    Tadalafil plasma concentrations declined nearly monoexponentially with a mean half-life of 17.5 hours, with 5th and 95th percentiles of 11.5 and 29.6 hours.
    primary_references
    Tadalafil pharmacokinetics in healthy subjects. (2006). https://pubmed.ncbi.nlm.nih.gov/16487221/ DOI: 10.1111/j.1365-2125.2005.02553.x
    route
    Oral
    tissue
    Plasma tadalafil pharmacokinetics

    Tadalafil: PDE5 occupancy, the cGMP route and three measured endpoints (2026-09-22) · lines 78–87

    Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata. Two references carry an unresolvable erratum and are recorded as corrected. Study-specific doses, effect sizes and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

    ## tadalafil-half-life Tadalafil plasma concentrations declined nearly monoexponentially with a mean half-life of 17.5 hours, with 5th and 95th percentiles of 11.5 and 29.6 hours. Model/species: 237 healthy subjects across 13 clinical pharmacology studies, with a separate multiple-dose study Tissue/system: Plasma tadalafil pharmacokinetics Exposure: Single 2.5 to 20 mg doses, and 10 or 20 mg once daily for 10 days Route: Oral Duration: Single dose and 10 days Limits: Healthy subjects only. No clinically meaningful effect of body mass index, age, gender or smoking was identified, and food had negligible effect on bioavailability. Primary reference: Tadalafil pharmacokinetics in healthy subjects. (2006). https://pubmed.ncbi.nlm.nih.gov/16487221/ DOI: 10.1111/j.1365-2125.2005.02553.x Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

  8. After tadalafil, sublingual nitroglycerin lowered standing systolic blood pressure below 85 mmHg in more subjects than after placebo at 4, 8 and 24 hours, with no difference at 48, 72 and 96 hours.

    Tadalafil → Standing systolic blood pressure source_derived_draftungraded
    Experimental context and source evidence
    duration
    Measured to 96 hours after the last tadalafil dose
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    experimental_model
    150 male subjects, randomised crossover with a 10 to 21 day washout
    exposure
    Seven consecutive daily doses of tadalafil 20 mg or placebo, then repeated sublingual nitroglycerin 0.4 mg
    limitations
    A pharmacodynamic interaction study in male volunteers using a fixed 20 mg dose; the time course reported here describes when the interaction was detectable, not a dosing instruction.
    organism
    150 male subjects, randomised crossover with a 10 to 21 day washout
    plain_language
    After tadalafil, sublingual nitroglycerin lowered standing systolic blood pressure below 85 mmHg in more subjects than after placebo at 4, 8 and 24 hours, with no difference at 48, 72 and 96 hours.
    primary_references
    Time course of the interaction between tadalafil and nitrates. (2003). https://pubmed.ncbi.nlm.nih.gov/14642699/ DOI: 10.1016/j.jacc.2003.09.023
    route
    Oral tadalafil with sublingual nitroglycerin
    tissue
    Standing systolic and diastolic blood pressure after a nitrate

    Tadalafil: PDE5 occupancy, the cGMP route and three measured endpoints (2026-09-22) · lines 89–98

    Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata. Two references carry an unresolvable erratum and are recorded as corrected. Study-specific doses, effect sizes and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

    ## tadalafil-augments-the-nitrate-blood-pressure-fall After tadalafil, sublingual nitroglycerin lowered standing systolic blood pressure below 85 mmHg in more subjects than after placebo at 4, 8 and 24 hours, with no difference at 48, 72 and 96 hours. Model/species: 150 male subjects, randomised crossover with a 10 to 21 day washout Tissue/system: Standing systolic and diastolic blood pressure after a nitrate Exposure: Seven consecutive daily doses of tadalafil 20 mg or placebo, then repeated sublingual nitroglycerin 0.4 mg Route: Oral tadalafil with sublingual nitroglycerin Duration: Measured to 96 hours after the last tadalafil dose Limits: A pharmacodynamic interaction study in male volunteers using a fixed 20 mg dose; the time course reported here describes when the interaction was detectable, not a dosing instruction. Primary reference: Time course of the interaction between tadalafil and nitrates. (2003). https://pubmed.ncbi.nlm.nih.gov/14642699/ DOI: 10.1016/j.jacc.2003.09.023 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

  9. Tadalafil increased six-minute walk distance in a dose-dependent manner in pulmonary arterial hypertension, with a mean placebo-corrected effect of 33 metres, and only the 40 mg dose met the prespecified level of statistical significance.

    Tadalafil → Six-minute walk distance source_derived_draftungraded
    Experimental context and source evidence
    duration
    16 weeks, double-blind placebo-controlled
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    experimental_model
    405 patients with idiopathic or associated pulmonary arterial hypertension, treatment-naive or on background bosentan
    exposure
    Tadalafil 2.5, 10, 20 or 40 mg once daily against placebo
    limitations
    The treatment effect was 44 metres in bosentan-naive patients and 23 metres with confidence intervals crossing zero in those already on bosentan, so the benefit on top of existing endothelin blockade was not established here. PubMed records an erratum for this paper without a resolvable identifier, so the erratum was not read and it is not known whether it altered these figures.
    organism
    405 patients with idiopathic or associated pulmonary arterial hypertension, treatment-naive or on background bosentan
    plain_language
    Tadalafil increased six-minute walk distance in a dose-dependent manner in pulmonary arterial hypertension, with a mean placebo-corrected effect of 33 metres, and only the 40 mg dose met the prespecified level of statistical significance.
    primary_references
    Tadalafil therapy for pulmonary arterial hypertension. (2009). https://pubmed.ncbi.nlm.nih.gov/19470885/ DOI: 10.1161/CIRCULATIONAHA.108.839274
    route
    Oral
    tissue
    Six-minute walk distance, WHO functional class and clinical worsening

    Tadalafil: PDE5 occupancy, the cGMP route and three measured endpoints (2026-09-22) · lines 100–109

    Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata. Two references carry an unresolvable erratum and are recorded as corrected. Study-specific doses, effect sizes and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

    ## tadalafil-six-minute-walk-in-pulmonary-arterial-hypertension Tadalafil increased six-minute walk distance in a dose-dependent manner in pulmonary arterial hypertension, with a mean placebo-corrected effect of 33 metres, and only the 40 mg dose met the prespecified level of statistical significance. Model/species: 405 patients with idiopathic or associated pulmonary arterial hypertension, treatment-naive or on background bosentan Tissue/system: Six-minute walk distance, WHO functional class and clinical worsening Exposure: Tadalafil 2.5, 10, 20 or 40 mg once daily against placebo Route: Oral Duration: 16 weeks, double-blind placebo-controlled Limits: The treatment effect was 44 metres in bosentan-naive patients and 23 metres with confidence intervals crossing zero in those already on bosentan, so the benefit on top of existing endothelin blockade was not established here. PubMed records an erratum for this paper without a resolvable identifier, so the erratum was not read and it is not known whether it altered these figures. Primary reference: Tadalafil therapy for pulmonary arterial hypertension. (2009). https://pubmed.ncbi.nlm.nih.gov/19470885/ DOI: 10.1161/CIRCULATIONAHA.108.839274 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

  10. Tadalafil 5 mg once daily improved the total International Prostate Symptom Score by a mean difference of 2.3 points against placebo in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

    Tadalafil → Total International Prostate Symptom Score source_derived_draftungraded
    Experimental context and source evidence
    duration
    12 weeks
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    experimental_model
    1500 men pooled from four international randomised placebo-controlled studies
    exposure
    Tadalafil 5 mg once daily against placebo
    limitations
    A pooled analysis rather than a single trial. Improvements were significant regardless of baseline symptom severity, age, recent alpha-blocker or PDE5 inhibitor use, total testosterone or predicted prostate volume, so no subgroup was identified in which the effect was absent, and the mechanism in this tissue is not established by the symptom score. PubMed records an erratum for this paper without a resolvable identifier, and the abstract itself carries an inline corrected marker, so it is not known whether the erratum altered these figures.
    organism
    1500 men pooled from four international randomised placebo-controlled studies
    plain_language
    Tadalafil 5 mg once daily improved the total International Prostate Symptom Score by a mean difference of 2.3 points against placebo in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.
    primary_references
    Efficacy and safety of tadalafil 5 mg once daily for lower urinary tract symptoms suggestive of benign prostatic hyperplasia. (2013). https://pubmed.ncbi.nlm.nih.gov/23876588/ DOI: 10.1016/j.urology.2013.05.005
    route
    Oral
    tissue
    Lower urinary tract symptoms

    Tadalafil: PDE5 occupancy, the cGMP route and three measured endpoints (2026-09-22) · lines 111–120

    Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata. Two references carry an unresolvable erratum and are recorded as corrected. Study-specific doses, effect sizes and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

    ## tadalafil-lowers-prostate-symptom-score Tadalafil 5 mg once daily improved the total International Prostate Symptom Score by a mean difference of 2.3 points against placebo in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Model/species: 1500 men pooled from four international randomised placebo-controlled studies Tissue/system: Lower urinary tract symptoms Exposure: Tadalafil 5 mg once daily against placebo Route: Oral Duration: 12 weeks Limits: A pooled analysis rather than a single trial. Improvements were significant regardless of baseline symptom severity, age, recent alpha-blocker or PDE5 inhibitor use, total testosterone or predicted prostate volume, so no subgroup was identified in which the effect was absent, and the mechanism in this tissue is not established by the symptom score. PubMed records an erratum for this paper without a resolvable identifier, and the abstract itself carries an inline corrected marker, so it is not known whether the erratum altered these figures. Primary reference: Efficacy and safety of tadalafil 5 mg once daily for lower urinary tract symptoms suggestive of benign prostatic hyperplasia. (2013). https://pubmed.ncbi.nlm.nih.gov/23876588/ DOI: 10.1016/j.urology.2013.05.005 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

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  • Tadalafil: PDE5 occupancy, the cGMP route and three measured endpoints (2026-09-22)Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata. Two references carry an unresolvable erratum and are recorded as corrected. Study-specific doses, effect sizes and limitations retained. Not publisher full text. · unverified_draftRead preserved source

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