Reference

Dynamic modeling of cortisol reduction after inhaled administration of fluticasone propionate

Dynamic modeling of cortisol reduction after inhaled administration of fluticasone propionate. Rohatagi, Shashank; Bye, Alan; Falcoz, Christine; Mackie, Alison E.; Meibohm, Bernd; Mollmann, Helmut; Derendorf, Hartmut (College Pharmacy, University Florida, Gainesville, FL 32610, USA). Journal of Clinical Pharmacology, 36(10), 938-941 (English) 1996 Lippincott-Raven. CODEN: JCPCBR. ISSN: 0091-2700. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) Fluticasone propionate (FP) is a new corticosteroid that has been developed for the treatment of asthma. The compd. has a very high receptor affinity, 18 times that of dexamethasone. After inhalation, FP is systemically available because of inhaled bioavailability. In healthy subjects this may lead to measurable systemic effects, such as cortisol redn. A clin. study was conducted in 12 healthy volunteers to det. the systemic effects after inhaled administration of single 500-mg, 1000-mg, and 2000-mg doses of FP. Blood samples were collected over a 24-h period after administration. Concns. of FP and cortisol were measured in plasma by immunoassay. 50-23-7 and 80474-14-2 which are cas registry numbers are also used here. Cortisol redn. was chosen as the pharmacodynamic parameter. A novel linear release rate model was used to parameterize the cortisol data. The pharmacokinetics of FP were linear over the dose range studied. The cortisol release parameters were detd. from baseline data (before drug administration). Based on these results, the E50 values for cortisol redn. were then detd. for each dose of FP. The av. E50 was 0.134 ng/mL for total FP concns. and 0.013 ng/mL for unbound FP concns.; these results were not dose dependent. These in vivo pharmacodynamic values measured in healthy subjects are in good agreement with the relatively high receptor affinity of FP. .

Pharmacokinetics and systemic effects of inhaled fluticasone propionate in healthy subjects

Pharmacokinetics and systemic effects of inhaled fluticasone propionate in healthy subjects. Thorsson, L.; Dahlstroem, K.; Edsbaecker, S.; Kaellen, A.; Paulson, J.; Wiren, J-E. (Astra Draco AB, Lund S-221 00, Swed.). British Journal of Clinical Pharmacology, 43(2), 155-161 (English) 1997 Blackwell. CODEN: BCPHBM. ISSN: 0306-5251. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) This study was undertaken to see whether the differences in plasma cortisol suppression caused by single and repeated administration of fluticasone propionate (FP) can be explained by systemic accumulation. Healthy subjects were given, in a crossover fashion, a single-dose inhalation (1000 mg) of FP and repeated inhalations (1000 mg twice daily) every 12 h during 7 days. There was a washout period of 2 wk between the treatments. An i.v. dose of 20 mg FP was given as a ref. Plasma concns. 80474-14-2 and 50-23-7 which are cas registry numbers are also used here. of FP after each treatment were detd. by liq. chromatog. plus tandem mass spectrometry. Plasma cortisol was detd. by immunoassay after the inhaled doses. The av. plasma concn. of FP was about 1.7 times higher after multiple inhalations than after a single dose. Systemic availability, mainly attributable to pulmonary deposition, was 15.6% of the nominal dose. Daytime plasma cortisol suppression vs. basal values was 47% and 95% for the single and repeated doses, resp. To conclude, a slow elimination of FP leads to accumulation during repeated administration. This accumulation may explain the marked decrease in plasma cortisol seen during treatment with fluticasone propionate within the clin. dose range. .