Cited by 125Adrenal Hormones and DisordersPharmacogenetics and Drug MetabolismPharmaceutical studies and practices

Prednisolone Pharmacokinetics and Pharmacodynamics in Relation to Sex and Race

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Magee, Mindy He, Blum, Robert A., Lates, Christian D., Jusko, William J.·2001·The Journal of Clinical Pharmacology

Abstract

Prednisolone pharmacokinetics (PK) and pharmacyodynamics (PD) were investigated in relation to sex and race in white males, black males, white females, and black females (n = 8/group) after a single oral dose (0.27 mg/kg) of prednisone. The study consisted of baseline and prednisone phases with 32‐hour sampling in each phase. Women were studied during the luteal phase of their menstrual cycle. Total and free plasma prednisolone concentrations were assayed by HPLC and ultrafiltration, and pharmacokinetic data were analyzed by compartmental fitting using WinNonlin. Plasma cortisol concentrations were assayed by HPLC; T‐helper, T‐suppressor lymphocyte, and neutrophil cell counts were determined by FACS and hemocytometry, and these pharmacodynamic data were evaluated by basic and extended indirect response models using ADAPT II. Total body weight‐normalized free prednisolone oral clearance and apparent volume of distribution were higher in men compared with women, regardless of race (by 22% in whites and 40% in blacks for oral clearance, p < 0.01; by 32% in whites and 38% in blacks for apparent volume of distribution, p < 0.01). The 50% inhibitory concentration (IC50) values for T‐suppressor cell‐trafficking inhibition were higher in whites than in blacks, regardless of sex (by 125% in men and 208% in women, p < 0.01). The IC50 or SC50 values for effects of prednisolone on cortisol secretion and T‐helper lymphocyte or neutrophil trafficking were not statistically different between men and women, blacks and whites. The findings of this study suggest that there are some prednisolone PK/PD differences related to sex and race. However, these differences do not suggest the need for dosage adjustments, and additional experiments with repeat dosing are needed to fully evaluate the clinical implication of these findings.

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  1. [14]Spahn JBE, Covar R, Leung D. Do African Americans display a diminished response to glucocorticoids? J Allergy Clin Immunology. 1999;104:S62. [Google Scholar]
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  3. [26]D’Argenio DZ, Schumitzky A. ADAPT II Users’ Guide: Pharmacokinetic/Pharmacodynamic Systems Analysis Software. Los Angeles: Biomedical Simulations Resource; 1997. [Google Scholar]

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Authors
Magee, M. H., Blum, R. A., Lates, C. D., & Jusko, W. J.
Affiliations
Kaleida Health (US)
Corresponding author
Jusko, William J.
Venue
The Journal of Clinical Pharmacology
Publisher
Wiley
Published
2001-11
Volume
41
Issue
11
Pages
1180-1194
ISSN
  • 0021-9754 (ISSN-L)
  • 0091-2700
  • 1552-4604
OpenAlex
W2065913585
Cited by
125
References
44
Citations by year
2026: 2 · 2025: 7 · 2024: 8 · 2023: 8 · 2022: 5 · 2021: 9 · 2020: 4 · 2019: 13 · 2018: 5 · 2017: 4 · 2016: 6 · 2015: 2 · 2014: 3 · 2013: 6 · 2012: 5
FWCI
4.14
Type
journal article
Language
en
Open access
Locations
  • The Journal of Clinical Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of General Medical Sciences (R37GM024211, GM 24211, R01GM024211)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
Keywords
prednisolone, pharmacokinetics, pharmacodynamics, sex differences, racial differences, prednisone, oral clearance, volume of distribution, cortisol secretion, T helper cells, T suppressor lymphocytes, neutrophil trafficking, indirect response model, dose adjustment
MeSH terms
Adolescent, Adult, Anti-Inflammatory Agents, Female, T-Lymphocytes, Helper-Inducer, Humans, Hydrocortisone, Male, Middle Aged, Neutrophils, Prednisolone, Sex Factors, Black People, White People, T-Lymphocytes, Regulatory

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