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.


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 m2) and methylprednisolone (40 mg/1.73 m2) 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.
Fost
D A
DA
Ira J. and Jacqueline Neimark Laboratory of Clinical Pharmacology in Pediatrics, Divisions of Clinical Pharmacology, Denver, CO, USA.
Leung
D Y
DY
Martin
R J
RJ
Brown
E E
EE
Szefler
S J
SJ
Spahn
J D
JD
D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism; D017291:Clarithromycin / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006801:Humans; D008775:Methylprednisolone / Q000097:blood / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D017291:Clarithromycin; D008775:Methylprednisolone