Pharmacokinetics and tissue distribution of a new mesalamine rectal gel in ulcerative colitis patients
Bibliographic record
Abstract
Objective Mesalamine (5-ASA) has a topical action in the treatment of ulcerative colitis (UC) but many adverse events are likely related to its systemic availability. It is therefore important to assess systemic exposure to 5-ASA and tissue concentrations produced by a new dosage form. This project assessed the pharmacokinetics (PK) of 5-ASA from a new rectal gel in UC patients. Methods 6 UC patients received a single 4 g dose of 5-ASA (Canasa-gel®) and, starting 48 hours later, 4 g HS x 4 days. Blood was collected at intervals for 30 hours and urine for 48 hours after first and last doses. Rectal biopsies were taken 8 hours after the last dose. 5-ASA was assayed by a fully validated LC-MS-MS method. Results After single dose, means (sd) were 2821 (1293) ng/mL for Cmax, 37638 (24370) ng h/mL for AUC0-∞, and 6.3 (8.2) h for half-life. After multiple doses means (sd) were 102 (152) ng/mL for Cmin, 2104 (743) ng/mL for Cmax, 21975 (10808) ng h/mL for AUC0-∞, and 4.0 (2.6) h for half-life. Mean (sd) total (unchanged and metabolized) urinary recovery of 5-ASA after single dose was 718 (388) mg. Mean (sd) rectal 5-ASA concentration was 25.2 (28.5) ng/mg tissue. Conclusion The pharmacokinetics from this new gel compare favorably with those from enema and suppository. It delivers adequate amount of 5-ASA to disease tissues. Based on PK, this new dosage form should be at least as safe and effective as enema and suppository. Clinical trials are required to confirm this conclusion. Clinical Pharmacology & Therapeutics (2004) 75, P38–P38; doi: 10.1016/j.clpt.2003.11.146
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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) | 0.001 | 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".