HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:
Sign In to gain access to subscriptions and/or personal tools.

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Request Reprints Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wu, K. Articles by Hochhaus, G. Search for Related Content PubMed PubMed Citation Articles by Wu, K. Articles by Hochhaus, G. Social Bookmarking                         What's this?

Evaluation of the Administration Time Effect on the Cumulative Cortisol Suppression and Cumulative Lymphocytes Suppression for Once-Daily Inhaled Corticosteroids: A Population Modeling/Simulation Approach

From Novartis, Cambridge, Massachusetts (Dr Wu); Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida (Dr Goyal, Dr Hochhaus); and CEDRA Corporation, Austin, Texas (Dr Stark).

Inhaled glucocorticoids continue to be first-line therapy in asthma. To improve improving patient compliance, newer inhaled glucocorticoids have been developed for once-a-day treatment. This study was interested in identifying the optimal time of dosing using 2 surrogate markers of glucocorticoid action. A previously published study on the pharmacokinetics and pharmacodynamics (cortisol and blood lymphocyte suppression) of the inhaled glucocorticoids budesonide and fluticasone propionate was reanalyzed using a population pharmacokinetic approach. A stochastic numerical simulation using NONMEM assessed the effects of time of dosing on cortisol (side effect parameter) and blood lymphocytes (side effect and effect parameter). The effects on cortisol were more pronounced when the glucocorticoids were given in the morning, whereas the effects on lymphocytes (an effect controlled by endogenous and exogenous glucocorticoids) were maximized when dosing occurred in the late afternoon or evening. Twice-daily dosing of the same dose resulted in smaller differences between maximum and minimal effects. These were of no clinical relevance. Simulations for once-daily dosing support clinical studies that reported a higher antiasthmatic effect and lower cortisol suppression when once-daily dosing occurs in the evening.

Key Words: corticosteroid • simulation • modeling • glucocorticoids • asthma

Address for reprints: Günther Hochhaus, PhD, University of Florida, Department of Pharmaceutics, Box 100494, Gainesville, FL 32610; e-mail: hochhaus{at}cop.ufl.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?