Biodistribution, plasma kinetics and quantification of single-pass pulmonary clearance of adrenomedullin
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Bibliographic record
Abstract
The biodistribution, pharmacokinetics and multi-organ clearance of the vasodilator peptide AM (adrenomedullin) were evaluated in rats and its single-pass pulmonary clearance was measured in dogs by the indicator-dilution technique. Intravenously administered 125I-rAM(1-50) [rat AM(1-50)] was rapidly cleared following a two-compartment model with a very rapid distribution half-life of 2.0 min [95% CI (confidence interval), 1.98-2.01] and an elimination half-life of 15.9 min (95% CI, 15.0-16.9). The lungs retained most of the injected activity with evidence of single-pass clearance, since retention was lower after intra-arterial (13.5+/-0.6%) compared with intravenous (30.4+/-1.5%; P < 0.001) injection. Lung tissue levels of total endogenous AM were 20-fold higher than in other organs with no difference in plasma levels across the pulmonary circulation. In dogs, there was 36.4+/-2.1% first-pass unidirectional extraction of 125I-rAM(1-50) by the lungs that was reduced to 21.9+/-2.4% after the administration of unlabelled rAM(1-50) (P < 0.01). Extraction was not affected by calcitonin-gene-related peptide administration (40.6+/-2.9%), but was slightly reduced by the C-terminal fragment of human AM(22-52) (31.4+/-3.3%; P < 0.01). These data demonstrate that the lungs are a primary site for AM clearance in vivo with approx. 36% first-pass extraction through specific receptors. This suggests that the lungs not only modulate circulating levels of this peptide, but also represent its primary target.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.003 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it