       Document 0430
 DOCN  M9620430
 TI    Pharmacodynamic model for joint exogenous and endogenous corticosteroid
       suppression of lymphocyte trafficking.
 DT    9602
 AU    Milad MA; Ludwig EA; Anne S; Middleton E Jr; Jusko WJ; Department of
       Pharmaceutics, School of Pharmacy, State University; of New York at
       Buffalo 14260, USA.
 SO    J Pharmacokinet Biopharm. 1994 Dec;22(6):469-80. Unique Identifier :
       AIDSLINE MED/96015276
 AB    The circadian pattern of the immune system correlates with that of
       circulating T-helper cells and inversely with cortisol concentrations.
       Corticosteroids, both endogenous and exogenous, cause lymphocyte
       dimunition in blood by retention of cells in the lymphatic circulation.
       A physiologic pharmacodynamic model was developed to describe changes in
       circulating lymphocytes as a function of both endogenous cortisol and
       methylprednisolone concentrations. The model was applied to T-helper and
       T-suppressor cell data collected from six asthmatic men during baseline,
       after single-dose, and after 6 days of 20 mg daily methylprednisolone.
       The model described all phases of the study well. Baseline circadian
       rhythm of lymphocytes was related to cortisol concentrations.
       Multiple-dosing of methylprednisolone caused apparent tolerance and
       decreased the sensitivity of lymphocytes to corticosteroids by 116% and
       markedly reduced endogenous cortisol concentrations. A 60% increase in
       circulating T-helper cells was observed which could be accounted for by
       dual changes in receptor sensitivity and endogenous cortisol.
 DE    Adrenal Cortex Hormones/*PHARMACOLOGY/*PHYSIOLOGY  Adult  Asthma/BLOOD
       Circadian Rhythm/PHYSIOLOGY  CD4-CD8 Ratio  Glucocorticoids,
       Synthetic/PHARMACOLOGY  Human  Hydrocortisone/PHARMACOLOGY  Lymphocyte
       Count/DRUG EFFECTS  Lymphocytes/*DRUG EFFECTS/*PHYSIOLOGY  Male
       Methylprednisolone/PHARMACOLOGY  Models, Biological  Support, Non-U.S.
       Gov't  Support, U.S. Gov't, P.H.S.  T-Lymphocytes, Helper-Inducer/DRUG
       EFFECTS/PHYSIOLOGY  CLINICAL TRIAL  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

