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AND THE ANSWERS ARE . . .

  1. Treatment with Cic in high doses affects the hypothalamic-pituitary adrenal (HPA) axis function significantly less commonly than do other ICS agents used in similar doses
    True
  2. Cic treatment is associated with a significant incidence of oral candidiasis
    False
  3. Cic cannot be used in combination with an inhaled long-acting beta agonist (LABA).
    False
  4. Cic metabolite is very highly bound to plasma proteins after systemic absorption
    True
  5. Cic must be administered by a power nebulizer
    False

Discussion
Cic is a very interesting compound which is actually a pro-drug, converted enzymatically into a metabolite with corticosteroid activity by enzymatic activity in the lower airways. Since there appears to be little or no such enxymatic conversion in the throat, subjects treated with inhaled Cic do not have increased incidence or oral candidiasis.

After the active corticosteroid metabolite binds strongly to receptors in the lower airways (and carries out anti-asthma effects), some is absorbed systemically. But here, another property of Cic reduces the potential for systemic adverse corticosteroid effects, The Cic metabolite which is absorbed systemically is rapidly and almost completely bound to plasma proteins and then rapidly disposed of. This degree of binding is greater than roughly 90% degree of binding of some other ICS agents to plasma proteins. Since it is only the non-protein bound ("free") corticosteroid which binds to receptors on target tissues, there is little adverse effects on the HPA axis with Cic treatment doses of up to 1250 microg/day. When asthmatic patients are treated with that dose of other ICS agents, suppression of the HPA axis function is sometimes observed.

Cic can be used in combination with inhaled LABA similar to the combination approach already used with certain other ICS agents such as budesonide or fluticasone. Indeed, trials of combination Cic-LABA therapy have been carried out. Cic administration does not require a power nebulizer. Several administration approaches, including a metered-dose inhaler using an HFA propellant, have been evaluated.

References

1. Drugs Today 2004 Jul;40:569-76
2 Respiratory Medicine 2006. Jan 18, E pub

 



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