Bioavailability and Pharmacokinetics of Dehydroepiandrosterone in the Cynomolgus Monkey
Bibliographic record
Abstract
We have studied the pharmacokinetics of dehydroepiandrosterone (DHEA) administered orally (PO), i.v., and during a continuous i.v. infusion in ovariectomized cynomolgus monkeys under suppression of adrenal DHEA secretion with dexamethasone. The glucocorticoid induced a rapid suppression of serum cortisol, DHEA, and DHEA-sulfate (DHEA-S) as well as their metabolites, thus permitting to use this model to study the pharmacokinetic parameters of DHEA and its metabolites without significant interference by endogenous steroid levels. After a single 10 mg i.v. dose of DHEA, the metabolic clearance rate and terminal half-life of DHEA were 99.9 +/- 9.1 liter/d and 4.5 +/- 0.3 h, respectively. Following a 50-mg DHEA PO dose, systemic availability was only 3.1 +/- 0.4%. As shown by their high conversion ratios, the major circulating metabolites of DHEA are DHEA-S, androsterone glucuronide, and androstane-3 alpha,17 beta-diol-glucuronide. The conversion ratios of androst-5-ene-3 beta,17 beta-diol, testosterone, dihydrotestosterone, and androstenedione are, in comparison, small. No transformation to estrogens could be detected in the circulation after either i.v. or PO DHEA administration. The present data indicate that DHEA is transformed predominantly into androgens in peripheral tissues in ovariectomized cynomolgus monkeys with minimal (androgens) or no (estrogens) release of the bioactive steroids in the circulation. Furthermore, the present study supports the importance of measuring circulating androgen glucuronide derivatives to assess hormonal exposure of peripheral tissues to androgens after DHEA administration.
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How this classification was reachedexpand
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 | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 teacher head, 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".