NDLI: Pharmacokinetic/Pharmacodynamic Modeling of Total Lymphocytes and Selected Subtypes After Oral Budesonide

Content Provider	Springer Nature Link
Author	Stark, Jeffrey G. Werner, Sybille Homrighausen, Susanne Tang, Yufei Krieg, Michael Derendorf, Hartmut Moellmann, Helmut Hochhaus, Guenther
Copyright Year	2006
Abstract	In the present pharmacokinetic/pharmacodynamic (PK/PD) evaluation, cortisol, total lymphocytes, and lymphocyte subpopulations were monitored following single oral doses of two oral formulations of 3 mg budesonide (BUD) (Dosage Forms A and B) in order to assess the differential effects that BUD may have on cortisol suppression and the modulation of blood lymphocyte subtypes. On a single occasion, five subjects received one 3 mg capsule of Dosage Form A, four received three capsules of Dosage Form A (single dose of 9 mg), and five received three capsules of Dosage Form B (single dose of 9 mg). Placebo capsules were administered to six subjects in the study. Cortisol concentrations, total lymphocyte counts, and lymphocyte subpopulation counts for the CD3, CD4, CD8, CD19, and CD56/16 were fitted to an in direct PK/PD response model that described the effects of BUD on serum cortisol concentrations as well as the combined effects of BUD and cortisol on total lymphocytes and the CD3, CD4, CD8, CD19, and CD56/16 subtypes. Data were also analyzed using noncompartmental methods. The PK/PD model fitted the data with the exception of data for CD56/16. The IC$_{50}$ value for unbound BUD acting on total lymphocytes was 0.276 ng/ml while the IC$_{50}$ values for unbound BUD acting on lymphocyte subtypes ranged from 0.150 ng/ml for CD4 to 0.364 ng/ml for CD8. The IC$_{50}$ values for the effects of BUD on serum cortisol were lower (0.079 ng/ml). The results of PK/PD modeling and noncompartmental analysis indicate that BUD has a smaller effect on the CD8 subtype and larger effects on the CD4 and CD19 subtypes, relative to the effect on total lymphocytes, and that cortisol suppression, although not a direct immunological biomarker, may be a more sensitive marker for the systemic effect of corticosteroids.
Starting Page	441
Ending Page	459
Page Count	19
File Format	PDF
ISSN	1567567X
Journal	Journal of Pharmacokinetics and Pharmacodynamics
Volume Number	33
Issue Number	4
e-ISSN	15738744
Language	English
Publisher	Kluwer Academic Publishers-Plenum Publishers
Publisher Date	2006-04-22
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	integrated PK/PD model corticosteroids serum cortisol suppression lymphocyte sub-populations Biomedical Engineering Biochemistry Veterinary Medicine Pharmacy Pharmacology/Toxicology
Content Type	Text
Resource Type	Article
Subject	Pharmacology

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