Lack of effect of zafirlukast on the pharmacokinetics of azithromycin, clarithromycin, and 14-hydroxyclarithromycin in healthy volunteers.
This randomized, open-label, crossover study was conducted to investigate whether the coadministration of zafirlukast would affect the pharmacokinetics of azithromycin, clarithromycin, or 14-hydroxyclarithromycin (14-OHC). Twelve healthy subjects (six males and six females) received single 500-mg doses of azithromycin and clarithromycin with and without zafirlukast given to a steady-state concentration. Blood was collected prior to all macrolide doses and for 3 and 10 days after each clarithromycin and azithromycin dose, respectively. Serum was assayed for azithromycin, clarithromycin, and 14-OHC concentrations by validated high-performance liquid chromatography assay systems. Data analyses were done by noncompartmental and nonparametric methods. Analysis of the patients indicated that the addition of steady-state concentrations of zafirlukast did not significantly alter the pharmacokinetic parameters of or overall exposure (based on the area under the concentration-time curve) to azithromycin, clarithromycin, and 14-OHC. While zafirlukast is a known inhibitor of CYP3A4, it does not appear to exert a clinically or statistically significant pharmacokinetic effect on azithromycin, clarithromycin, or 14-OHC.
Garey
K W
KW
Department of Pharmacy, Bassett Healthcare, Cooperstown, New York, USA.
Peloquin
C A
CA
Godo
P G
PG
Nafziger
A N
AN
Amsden
G W
GW
D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D017963:Azithromycin / Q000493:pharmacokinetics*; D017291:Clarithromycin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007211:Indoles; D020024:Leukotriene Antagonists / Q000008:administration & dosage*; D008297:Male; D048448:Phenylcarbamates; D013449:Sulfonamides; D014105:Tosyl Compounds / Q000008:administration & dosage*
D018927:Anti-Asthmatic Agents; D000900:Anti-Bacterial Agents; D007211:Indoles; D020024:Leukotriene Antagonists; D048448:Phenylcarbamates; D013449:Sulfonamides; D014105:Tosyl Compounds; C056228:14-hydroxyclarithromycin; D017963:Azithromycin; D017291:Clarithromycin; C062735:zafirlukast