Inhaled Corticosteroid Use in HIV-positive Individuals Taking Protease Inhibitors

A Review of Pharmacokinetics, Case Reports and Clinical Management

P Saberi; T Phengrasamy; DP Nguyen


HIV Medicine. 2013;14(9):519-529. 

In This Article

Pharmacokinetics of Corticosteroid Inhalers

In the absence of sufficient studies on drug–drug interactions between inhaled/intranasal corticosteroids and PIs, consideration of key pharmacokinetic properties may help us to elucidate which agents may be safer to use when the combination of these two classes is necessary. The extent of corticosteroid metabolism by the CYP3A4 isozyme is a critical factor in determining whether it will be affected by PIs and other CYP3A4 inhibitors. Other important properties that may minimize this drug–drug interaction include:[1] less systemic exposure as measured by glucocorticosteroid relative receptor binding affinity (RRA), which can translate to decreased nasal passage and lung receptor binding and decreased potency;[2] lower systemic oral bioavailability (systemic oral bioavailability is the extent to which the drug reaches the blood);[3] higher plasma protein binding (Pb), which results in a lower fraction of unbound drug and prevents diffusion of the drug into the tissue;[4] a shorter elimination half-life, which is determined by the volume of distribution and clearance of the drug; and[5] lower lipophilicity, which translates to lower distribution and binding of the drug to the tissue.[2]

In Table 1 we summarize and compare pertinent characteristics of inhaled/intranasal corticosteroids in order to identify those that may have a low risk of interaction and adverse effects. Among the available inhaled/intranasal corticosteroids, flunisolide and beclomethasone seem to meet most of the properties mentioned above, such as low RRA, low lipophilicity, short elimination half-life, and less dependence on metabolism by the CYP3A4 isozyme. Of the available corticosteroids, fluticasone exhibits the greatest suppressive effect on the hypothalamic-pituitary-adrenal axis.[3] This is probably a result of its pharmacokinetic properties, such as higher lipophilicity, a longer elimination half-life and a higher glucocorticoid RRA, as well as its relatively exclusive metabolism by CYP3A4.[4–7]