- Congenital adrenal hyperplasia (CAH) is the most common form of adrenal insufficiency in childhood; it requires cortisol replacement therapy with hydrocortisone (HC, synthetic cortisol) from birth and therapy monitoring for successful treatment. In children, the less invasive dried blood spot (DBS) sampling with whole blood including red blood cells (RBCs) provides an advantageous alternative to plasma sampling.
Potential differences in binding/association processes between plasma and DBS however need to be considered to correctly interpret DBS measurements for therapy monitoring. While capillary DBS samples would be used in clinical practice, venous cortisol DBS samples from children with adrenal insufficiency were analyzed due to data availability and to directly compare and thus understand potential differences between venous DBS and plasma. A previously published HC plasma pharmacokinetic (PK) model was extended by leveraging these DBS concentrations.
In addition to previously characterized binding of cortisol to albuminCongenital adrenal hyperplasia (CAH) is the most common form of adrenal insufficiency in childhood; it requires cortisol replacement therapy with hydrocortisone (HC, synthetic cortisol) from birth and therapy monitoring for successful treatment. In children, the less invasive dried blood spot (DBS) sampling with whole blood including red blood cells (RBCs) provides an advantageous alternative to plasma sampling.
Potential differences in binding/association processes between plasma and DBS however need to be considered to correctly interpret DBS measurements for therapy monitoring. While capillary DBS samples would be used in clinical practice, venous cortisol DBS samples from children with adrenal insufficiency were analyzed due to data availability and to directly compare and thus understand potential differences between venous DBS and plasma. A previously published HC plasma pharmacokinetic (PK) model was extended by leveraging these DBS concentrations.
In addition to previously characterized binding of cortisol to albumin (linear process) and corticosteroid-binding globulin (CBG; saturable process), DBS data enabled the characterization of a linear cortisol association with RBCs, and thereby providing a quantitative link between DBS and plasma cortisol concentrations. The ratio between the observed cortisol plasma and DBS concentrations varies highly from 2 to 8. Deterministic simulations of the different cortisol binding/association fractions demonstrated that with higher blood cortisol concentrations, saturation of cortisol binding to CBG was observed, leading to an increase in all other cortisol binding fractions.
In conclusion, a mathematical PK model was developed which links DBS measurements to plasma exposure and thus allows for quantitative interpretation of measurements of DBS samples.…
MetadatenAuthor details: | Viktoria Stachanow, Uta Neumann, Oliver BlankensteinGND, Davide BindelliniORCiD, Johanna MelinORCiD, Richard Ross, Martin J. J. Whitaker, Wilhelm HuisingaORCiDGND, Robin Michelet, Charlotte KloftORCiDGND |
---|
DOI: | https://doi.org/10.3389/fphar.2022.819590 |
---|
ISSN: | 1663-9812 |
---|
Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/35370666 |
---|
Title of parent work (English): | Frontiers in pharmacology |
---|
Subtitle (English): | a model-based analysis |
---|
Publisher: | Frontiers Media |
---|
Place of publishing: | Lausanne |
---|
Publication type: | Article |
---|
Language: | English |
---|
Date of first publication: | 2022/03/17 |
---|
Publication year: | 2022 |
---|
Release date: | 2024/06/03 |
---|
Tag: | adrenal insufficiency; association; binding; cortisol; dried blood spots; pediatrics; pharmacokinetics; red blood cells |
---|
Volume: | 13 |
---|
Article number: | 819590 |
---|
Number of pages: | 8 |
---|
Funding institution: | Freie Universitaet and Diurnal; Diurnal Lt |
---|
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Mathematik |
---|
DDC classification: | 5 Naturwissenschaften und Mathematik / 51 Mathematik / 510 Mathematik |
---|
| 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
---|
Peer review: | Referiert |
---|
Publishing method: | Open Access / Gold Open-Access |
---|
| DOAJ gelistet |
---|
License (German): | CC-BY - Namensnennung 4.0 International |
---|