Inhibition of methylprednisolone elimination in the presence of clarithromycin therapy

Background: Macrolide antibiotics have long been used as steroid-sparing agents in patients with severe steroid-dependent asthma. Their efficacy and their propensity to potentiate glucocorticoid adverse effects have been attributed in part to their ability to delay glucocorticoid clearance. Objectiv...

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Bibliographic Details
Published in:Journal of allergy and clinical immunology 1999-06, Vol.103 (6), p.1031-1035
Main Authors: Fost, David A., Leung, Donald Y.M., Martin, Richard J., Brown, Eleanor E., Szefler, Stanley J., Spahn, Joseph D.
Format: Article
Language:English
Subjects:
Adult
Anti-Bacterial Agents - therapeutic use
asthma
Asthma - drug therapy
Asthma - metabolism
Biological and medical sciences
clarithromycin
Clarithromycin - therapeutic use
Drug Therapy, Combination
Drug toxicity and drugs side effects treatment
Glucocorticoids
Humans
Medical sciences
methylprednisolone
Methylprednisolone - blood
Methylprednisolone - pharmacokinetics
Miscellaneous (drug allergy, mutagens, teratogens...)
pharmacokinetics
Pharmacology. Drug treatments
prednisone
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Summary:Background: Macrolide antibiotics have long been used as steroid-sparing agents in patients with severe steroid-dependent asthma. Their efficacy and their propensity to potentiate glucocorticoid adverse effects have been attributed in part to their ability to delay glucocorticoid clearance. Objective: We sought to determine whether clarithromycin, a newer macrolide antibiotic, can alter the pharmacokinetic profile of oral glucocorticoids and thereby increase the risk of steroid-induced adverse effects. Methods: An open-label study in a paired design (before and after treatment) was conducted in a hospital-based outpatient clinic. Participants were 6 adult patients (mean age, 30 years) with mild-to-moderate asthma. Prednisone (40 mg/1.73 m 2) and methylprednisolone (40 mg/1.73 m 2) were given as single randomized doses on consecutive study days before and on days 8 and 9 of a clarithromycin (500 mg twice daily) course. Twelve-hour pharmacokinetic profiles with measurement of plasma methylprednisolone and prednisolone levels were taken before and after clarithromycin therapy. Results: Clarithromycin therapy resulted in a 65% reduction of methylprednisolone clearance and significantly higher mean plasma methylprednisolone concentrations compared with preclarithromycin concentrations but had no significant effect on prednisolone clearance or mean prednisolone plasma concentrations. Conclusions: Clinicians must be aware of potential drug interactions that could place patients at increased risk for steroid-induced adverse effects. Such an effect has been demonstrated between clarithromycin and methylprednisolone, two drugs that may be administered concomitantly in asthma. To avoid potential steroid-enhancing effects, prednisone should be substituted for methylprednisolone during prolonged courses of clarithromycin therapy. (J Allergy Clin Immunol 1999;103:1031-5.)
ISSN:0091-6749
1097-6825
DOI:10.1016/S0091-6749(99)70175-2