Lack of pharmacokinetic drug-drug interaction between ciclesonide and erythromycin.
OBJECTIVE
To investigate whether systemic exposure to desisobutyrylciclesonide (des-CIC) (the pharmacologically active metabolite of ciclesonide) and erythromycin are affected by combined administration of ciclesonide and erythromycin.


METHODS
18 healthy subjects were enrolled in a Phase 1, open-label, randomized, three-period crossover study. Each subject received ciclesonide (640 microg ex-actuator, equivalent to 800 microg ex-valve, via hydrofluoroalkane metered-dose inhaler) and erythromycin (500 mg PO), separately and in combination, in random order. Blood samples were collected at timed intervals to determine serum concentrations of erythromycin, des-CIC, and ciclesonide using HPLC-MS detection. Adverse events were recorded throughout the study.


RESULTS
Combined administration of ciclesonide and erythromycin did not alter the pharmacokinetics (PK) of either drug. The serum concentration vs. time profiles of erythromycin, des-CIC, and ciclesonide were similar when ciclesonide and erythromycin were administered separately or together. In addition, the PK characteristics of erythromycin and des-CIC were equivalent following single or co-administration. Point estimates (90% confidence intervals (CI)) for erythromycin were as follows: AUC0-inf, 0.96 (0.79, 1.18); Cmax, 1.00 (0.84, 1.20); and t1/2, 0.96 (0.83, 1.12). The following point estimates (90% CI) were obtained for des-CIC: AUC0-inf, 1.16 (1.03, 1.30); Cmax, 1.06 (0.98, 1.15); and t1/2, 1.04 (0.96, 1.13). Lack of ciclesonide/erythromycin interaction was demonstrated as the 90% CI of AUC0-inf, Cmax, and t1/2 of both compounds were entirely within the stipulated equivalence range of 0.67 - 1.50. No study drug-related adverse events occurred during this study.


CONCLUSIONS
Combined administration of ciclesonide and erythromycin did not alter the PK properties of either drug. Both drugs were safe and well-tolerated. Therefore, systemic exposure to ciclesonide or erythromycin is not increased in patients receiving concomitant therapy.
Nave
R
R
ALTANA Pharma AG Konstanz, Germany. ruediger.nave@altanapharma.com
Drollmann
A
A
Steinijans
V W
VW
Zech
K
K
Bethke
T D
TD
D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D004347:Drug Interactions; D004917:Erythromycin / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D011282:Pregnenediones / Q000009:adverse effects / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D011282:Pregnenediones; D004917:Erythromycin; C120481:ciclesonide