An interactive algorithm for the assessment of cumulative cortisol suppression during inhaled corticosteroid therapy.
The objective of the study was to develop an algorithm based on a pharmacokinetic-pharmacodynamic (PK/PD) modeling approach to quantify and predict cumulative cortisol suppression (CCS) as a surrogate marker for the systemic activity of inhaled corticosteroid therapy. Two Excel spreadsheets, one for single dose and another for steady-state multiple doses of inhaled steroids, were developed for predicting CCS. Four of the commonly used inhaled steroids were chosen for the purposes of simulation: fluticasone propionate (FP), budesonide (BUD), flunisolide (FLU), and triamcinolone acetonide (TAA). Drug-specific PK and PD parameters were obtained from previous single- and multiple-dose studies. In cases in which multiple-dose data were not available, the single-dose data were extrapolated. The algorithm was designed to calculate CCS based on 5 input parameters: name of drug, dose, dosing interval, time(s) of dosing, and type of inhaler device. In addition, a generalized algorithm was set up to calculate CCS based on clearance, volume of distribution, absorption rate, protein binding, pulmonary deposition, oral bioavailability, and unbound EC50 of the corticosteroid of interest. The spreadsheet allowed predictions of CCS for single doses as well as steady-state conditions. A simple method has been developed that facilitates comparisons between various drugs and dosing regimens and has the potential to significantly reduce the number of comparative clinical trials to be performed for evaluating the short-term systemic activity of inhaled corticosteroids.
Krishnaswami
S
S
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL 32610-0494, USA.
Hochhaus
G
G
Derendorf
H
H
D000280:Administration, Inhalation; D000287:Administration, Topical; D000465:Algorithms; D000730:Androstadienes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019819:Budesonide / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D003864:Depression, Chemical; D005446:Fluocinolone Acetonide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D000068298:Fluticasone; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008954:Models, Biological; D009330:Nebulizers and Vaporizers; D014222:Triamcinolone Acetonide / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D005446:Fluocinolone Acetonide; D019819:Budesonide; C007734:flunisolide; D000068298:Fluticasone; D014222:Triamcinolone Acetonide; D006854:Hydrocortisone