Drug-drug Interaction Study of an Antimigraine Agent and Erythromycin

• Activity Number: 307
• Type: Contributed
• Date/Time: Wednesday, August 11, 2004 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Meiyu Shen*+ and Stella G. Machado
• Companies: U.S. Food and Drug Administration and U.S. Food and Drug Administration
• Keywords: antimigraine ; PK-PD modeling ; Drug-drug interaction

Abstract

Two studies were used to evaluate the potential elevation of diastolic blood pressure due to the administration of an antimigraine agent and erythromycin. The pharmacokinetic-pharmacodynamic (PK/PD) study of the antimigraine agent alone was a four-period crossover study. Fifteen subjects randomly received placebo plus the antimigraine agent at three of the following doses: 30, 60, 90, and 120 mg. The drug-drug interaction study was also a crossover study, 18 subjects randomly assigned to two groups, the first receiving 80 mg of the antimigraine agent, the second receiving 80 mg of the antimigraine agent plus erythromycin. After a washout period, both groups were then given the alternative treatment. The blood plasma concentration of the antimigraine agent and the diastolic blood pressure (DBP) were simultaneously measured at predetermined times. The pharmacodynamic measurement of interest for each patient was the maximum DPB change from baseline. The change in PK/PD of the antimigraine agent due to coadministration with erythromycin was assessed using general linear models. Plasma concentration of the antimigraine agent was elevated when co-administered with erythromycin.