ArticleBritish journal of clinical pharmacology2021
An integrated PK-PD model for cortisol and the 17-hydroxyprogesterone and androstenedione biomarkers in children with congenital adrenal hyperplasia.
Article in British journal of clinical pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- Crinecerfont Lowers Elevated Hormone Markers in Adults With 21-Hydroxylase Deficiency Congenital Adrenal Hyperplasia.The Journal of clinical endocrinology and metabolism · 2022Trial
- Mapping of sex hormones in the testicular vein of healthy men.The Journal of clinical endocrinology and metabolism · 2026Article
- Glucocorticoid reduction after starting crinecerfont in pediatric patients with classic congenital adrenal hyperplasia: practical perspectives.The Journal of clinical endocrinology and metabolism · 2026Review
- Evaluation of Sleep Health in Children With Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency.The Journal of clinical endocrinology and metabolism · 2025Article
- Anastrozole Improves Height Outcomes in Growing Children With Congenital Adrenal Hyperplasia Due to 21-hydroxylase Deficiency.The Journal of clinical endocrinology and metabolism · 2025Article
- Future Directions in the Management of Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency.The Journal of clinical endocrinology and metabolism · 2025Review
- A quantitative modeling framework to understand the physiology of the hypothalamic-pituitary-adrenal axis and interaction with cortisol replacement therapy.Journal of pharmacokinetics and pharmacodynamics · 2024Article
- Crinecerfont, a CRF1 Receptor Antagonist, Lowers Adrenal Androgens in Adolescents With Congenital Adrenal Hyperplasia.The Journal of clinical endocrinology and metabolism · 2023Article
- Interpretation of Steroid Biomarkers in 21-Hydroxylase Deficiency and Their Use in Disease Management.The Journal of clinical endocrinology and metabolism · 2023Review
- Model-Informed Target Morning 17α-Hydroxyprogesterone Concentrations in Dried Blood Spots for Pediatric Congenital Adrenal Hyperplasia Patients.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Depressive and anxiety disorders and antidepressant prescriptions among insured children and young adults with congenital adrenal hyperplasia in the United States.Frontiers in endocrinology · 2023Article
- Case Report: Anastrozole as a monotherapy for pre-pubertal children with non-classic congenital adrenal hyperplasia.Frontiers in endocrinology · 2023Article
- Analysis of therapy monitoring in the International Congenital Adrenal Hyperplasia Registry.Clinical endocrinology · 2022Article
- Article
- Diurnal salivary androstenedione and 17-hydroxyprogesterone levels in healthy volunteers for monitoring treatment efficacy of patients with congenital adrenal hyperplasia.Clinical endocrinology · 2022Article
- A 4-hour Profile of 17-hydroxyprogesterone in Salt-wasting Congenital Adrenal Hyperplasia: Is the Serial Monitoring Strategy Worth the Effort?Journal of clinical research in pediatric endocrinology · 2022Article
- Optimizing the Timing of Highest Hydrocortisone Dose in Children and Adolescents With 21-Hydroxylase Deficiency.The Journal of clinical endocrinology and metabolism · 2022Article
- Applications of cosinor rhythmometry in pharmacology.Journal of pharmacokinetics and pharmacodynamics · 2021Article
- Application of Deep Neural Networks as a Prescreening Tool to Assign Individualized Absorption Models in Pharmacokinetic Analysis.Pharmaceutics · 2021Article
- An integrated PK-PD model for cortisol and the 17-hydroxyprogesterone and androstenedione biomarkers in children with congenital adrenal hyperplasia.British journal of clinical pharmacology · 2021Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
aimsThe aim of this study was to characterize the pharmacokinetic/pharmacodynamic relationships of cortisol and the adrenal biomarkers 17-hydroxyprogesterone and androstenedione in children with congenital adrenal hyperplasia (CAH).
methodsA nonlinear mixed-effect modelling approach was used to analyse cortisol, 17-hydroxyprogesterone and androstenedione concentrations obtained over 6 hours from children with CAH (n = 50). A circadian rhythm was evident and the model leveraged literature information on circadian rhythm in untreated children with CAH. Indirect response models were applied in which cortisol inhibited the production rate of all three compounds using an I
resultsCortisol was characterized by a one-compartment model with apparent clearance and volume of distribution estimated at 22.9 L/h/70 kg and 41.1 L/70 kg, respectively. The IC
conclusionRapidly changing biomarker responses to cortisol concentrations highlight that single measurements provide volatile information about a child's disease control. Our model closely captured observed cortisol, 17-hydroxyprogesterone and androstenedione concentrations. It can be used to predict concentrations over 24 hours and allows many novel exposure metrics to be calculated, e.g., AUC, AUC-above-threshold, time-within-range, etc. Our long-range goal is to uncover dose-exposure-outcome relationships that clinicians can use in adjusting hydrocortisone dose and timing.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.