PHARMACOKINETIC AND PHARMACODYNAMIC EVALUATION OF TRIAMCINOLONE ACETONIDE AFTER INTRAVENOUS, ORAL, AND INHALED ADMINISTRATION

Triamcinolone acetonide (TCA) is a corticosteroid that is frequently u sed in the treatment of asthma. After inhalation, TCA can become syste mically available when the inhaled formulation is swallowed, causing u ndesirable systemic effects. A clinical study was conducted to determi ne the systemic side effects of TCA after intravenous (2 mg as phospha te ester), oral (5 mg), and inhaled (2 mg) administration. Blood sampl es were collected at appropriate times over 24 hours, and TCA concentr ations in plasma were measured by high-performance liquid chromatograp hy and radioimmunoassay. Free drug concentrations were determined by u ltrafiltration for correlating pharmacokinetics and pharmacodynamics. The free fraction of TCA (+/- standard deviation) was 29.0 +/- 1.3% an d was independent of the investigated concentration range up to 1,000 ng/mL. Pharmacodynamic parameters were determined by monitoring lympho cytes, granulocytes, and cortisol. Pharm acokinetic/pharmacodynamic mo deling was performed using a modified E(max) model for lymphocytes and granulocytes. A novel linear release rate model was used to character ize the cortisol data. The E(50) values determined from all three phar macodynamic endpoints were not significantly different for the three t reatments, indicating that these effects can be explained based on sys temic steroid concentrations.