التفاصيل البيبلوغرافية
| العنوان: |
Four-Compartment Diffusion Model of Cortisol Disposition: Comparison With 3 Alternative Models in Current Clinical Use. |
| المؤلفون: |
Dorin, Richard I, Urban, Frank K, Perogamvros, Ilias, Qualls, Clifford R |
| المصدر: |
Journal of the Endocrine Society; Feb2023, Vol. 7 Issue 2, p1-13, 13p |
| مصطلحات موضوعية: |
FICK'S laws of diffusion, HYDROCORTISONE, METABOLIC clearance rate |
| مستخلص: |
Context Estimated rates of cortisol elimination and appearance vary according to the model used to obtain them. Generalizability of current models of cortisol disposition in healthy humans is limited. Objective Development and validation of a realistic, mechanistic model of cortisol disposition that accounts for the major factors influencing plasma cortisol concentrations in vivo (Model 4), and comparison to previously described models of cortisol disposition in current clinical use (Models 1-3). Methods The 4 models were independently applied to cortisol concentration data obtained for the hydrocortisone bolus experiment (20 mg) in 2 clinical groups: healthy volunteers (HVs, n = 6) and corticosteroid binding globulin (CBG)–deficient (n = 2). Model 4 used Fick's first law of diffusion to model free cortisol flux between vascular and extravascular compartments. Pharmacokinetic parameter solutions for Models 1-4 were optimized by numerical methods, and model-specific parameter solutions were compared by repeated measures analysis of variance. Models and respective parameter solutions were compared by mathematical and simulation analyses, and an assessment tool was used to compare performance characteristics of the four models evaluated herein. Results Cortisol half-lives differed significantly between models (all P <.001) with significant model–group interaction (P =.02). In comparative analysis, Model 4 solutions yielded significantly reduced free cortisol half-life, improved fit to experimental data (both P <.01), and superior model performance. Conclusion The proposed 4-compartment diffusion model (Model 4) is consistent with relevant experimental observations and met the greatest number of empiric validation criteria. Cortisol half-life solutions obtained using Model 4 were generalizable between HV and CBG-deficient groups and bolus and continuous modes of hydrocortisone infusion. [ABSTRACT FROM AUTHOR] |
|
Copyright of Journal of the Endocrine Society is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Full Text Finder