THE CLINICAL-PHARMACOLOGY OF FLUTICASONE PROPIONATE

Fluticasone propionate is an inhaled corticosteroid with high antiinfl ammatory potency, used for the topical treatment of asthma. Its high l ipophilicity and associated low aqueous solubility result in high conc entrations in pulmonary tissue as well as a delayed absorption from th e lung into the systemic circulation after inhaled administration. Ora l bioavailability is negligible due to incomplete absorption and high first-pass inactivation, and systemic availability after inhalation is limited to the fraction absorbed from the lung. Removal from the syst emic circulation occurs rapidly by hepatic metabolism to an inactive d erivative, and systemic blood clearance approaches liver blood flow. E xcretion of the parent drug and its metabolite occurs nearly exclusive ly into the faeces, with negligible contribution of the renal pathway. Fluticasone propionate is extensively distributed throughout the body . The high volume of distribution results in low systemic concentratio ns and an elimination half-life of 7.8 h after intravenous administrat ion. After inhalation of therapeutic doses, fluticasone propionate fol lows linear pharmacokinetics with peak plasma concentrations in the pi cogram range, a prolonged terminal half-life of 11-14 h due to slow dr ug absorption, and a moderate accumulation during multiple dosing. Flu ticasone propionate suppresses the hypothalamic-pituitary-adrenal axis in a dose-dependent manner, but suppression seems to be less pronounc ed in asthmatic patients than implied by currently available data from healthy subjects. Fluticasone propionate represents a well-designed t opical corticosteroid, well-suited for inhalation therapy of asthma, w ith a good benefit-to-risk ratio and reliable therapeutic efficacy.