What is the difference in systemic absorption between oral prednisone and Inhaled Corticosteroids (ICS)?

From the Guidelines

Oral prednisone has significantly higher systemic absorption compared to inhaled corticosteroids (ICS). When prednisone is taken orally, it undergoes first-pass metabolism in the liver but still results in high bioavailability, leading to substantial systemic exposure and potential side effects. In contrast, ICS medications are designed to work directly in the lungs with minimal systemic absorption. According to the expert panel report 3 (epr-3): guidelines for the diagnosis and management of asthma-summary report 2007 1, the use of spacers or VHCs with MDIs can decrease oropharyngeal deposition and thus decrease the risk of topical side effects, and also reduce the potential systemic availability of ICSs with higher oral absorption.

The key differences between oral prednisone and ICS in terms of systemic absorption are:

• Bioavailability: Oral prednisone has a bioavailability of approximately 70-80%, while ICS medications have bioavailability ranging from less than 1% to about 20% 1.
• Systemic exposure: Oral prednisone results in substantial systemic exposure, leading to potential side effects like adrenal suppression, weight gain, mood changes, and osteoporosis with prolonged use.
• Localized action: ICS medications are designed to work directly in the lungs, reducing systemic side effects.

It's worth noting that high doses of ICS administered for prolonged periods may be associated with some systemic effects, such as posterior subcapsular cataracts or reduced bone density 1. However, these effects are generally much less pronounced than with oral corticosteroids. The use of ICS is preferred for long-term maintenance therapy in conditions like asthma and COPD, while oral prednisone is typically reserved for short courses during acute exacerbations.

From the FDA Drug Label

The therapeutic effects of conventional doses of orally inhaled budesonide are largely explained by its direct local action on the respiratory tract To confirm that systemic absorption is not a significant factor in the clinical efficacy of inhaled budesonide, a clinical study in adult patients with asthma was performed comparing 400 mcg budesonide administered via a pressurized metered dose inhaler with a tube spacer to 1400 mcg of oral budesonide and placebo The study demonstrated the efficacy of inhaled budesonide but not orally administered budesonide, even though systemic budesonide exposure was comparable for both treatments, indicating that the inhaled treatment is working locally in the lung. ALVESCO will often help control asthma symptoms with less suppression of HPA function than therapeutically similar oral doses of prednisone.

The systemic absorption of oral prednisone is significantly higher compared to inhaled corticosteroids (ICS) like budesonide and ciclesonide.

• Oral prednisone has a higher systemic absorption due to its oral administration route.
• Inhaled corticosteroids (ICS), on the other hand, have a lower systemic absorption due to their local action in the lungs and extensive first-pass hepatic degradation. The difference in systemic absorption between oral prednisone and ICS is significant, with ICS having a more localized effect on the respiratory tract and less impact on the hypothalamic-pituitary-adrenal (HPA) axis compared to oral prednisone 2 3.

From the Research

Systemic Absorption of Oral Prednisone vs. Inhaled Corticosteroids (ICS)

• The systemic absorption of oral prednisone is significantly higher compared to inhaled corticosteroids (ICS) 4.
• Oral corticosteroids have well-established systemic effects, whereas ICS have relatively minor and localized adverse effects, but can still cause systemic effects such as affecting the hypothalamo-pituitary-adrenal axis, bone density, and growth 5.
• The systemic bioavailability of ICS is reduced due to the lung's first-pass metabolism, but systemic absorption still occurs via the lung 6.
• Studies have shown that ICS can be as effective as oral prednisone in controlling asthma, with a daily dose of 400 μg of inhaled drug being approximately equivalent to 7.5 mg daily of prednisone 4.
• Inhaled steroids have been found to be better tolerated than oral prednisone, with a lower incidence of systemic unwanted effects 4, 7.
• The choice between oral prednisone and ICS depends on the individual patient's needs, with ICS being preferred for long-term maintenance treatment and oral prednisone being used for acute exacerbations 4.
• Different ICS molecules have varying levels of systemic effects, with fluticasone being more likely to cause systemic effects compared to budesonide, and newer molecules like ciclesonide potentially reducing systemic complications 5.