The Renal Handling of Tienilic Acid (Ticrynafen), a New Diuretic with Uricosuric Properties
Bibliographic record
Abstract
Tienilic acid (ticrynafen) [2,3-dichloro-4-(2-thyenil-carbonyl) phenoxyacetic acid] is a new diuretic with uricosuric properties in man and dog. In this animal the drug acts by blocking tubular transport of uric acid in the proximal tubule. We have demonstrated that tienilic acid (TA) is highly bound to plasma proteins at 37 ¤C (more than 95% at drug concentrations of 3.0–20.0 mg/dl). Thus, glomerular filtration of the drug is negligible and tienilic acid must reach the kidney at the antiluminal site of the tubule. During free-flow studies, the clearance of tienilic acid at stable plasma concentrations ranging from 3.0 to 20.0 mg/dl ranged from 11 to 22% of glomerular filtration measured by exogenous creatinine clearance. These values are 3–5 times greater than that accounted for by filtration of the drug alone and are highly suggestive of tubular secretion. Secretion becomes more apparent during alkalinization of the urine when the clearance of tienilic acid may rise to 40 and even 100% of glomerular filtration. During stop-flow studies, the urine over plasma ratio of the drug (U/P TA) over that of creatinine (U/P Cr) decreased along the nephron indicating progressive reabsorption. At equivalent plasma concentration, it was demonstrated that tienilic acid markedly depresses PAH transport in the proximal tubule. When plasma tienilic acid concentration is kept low (5 mg/dl) and PAH concentration is raised to 30 mg/dl, the (U/P TA)/(U/P Cr) drops by 50%. Our results indicate active secretion of tienilic acid in the proximal tubule followed by passive pH dependent reabsorption along the nephron. The drug is transported through the common organic acid pathway by a carrier having higher affinity for tienilic acid than for PAH.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".