Coadministration of nefazodone and desipramine: a pharmacokinetic interaction study.

OBJECTIVE To determine the potential for pharmacokinetic interaction between nefazodone (NFZ), and desipramine (DMI). METHOD A single center, open-label, multiple-dose, parallel-group pharmacokinetic trial conducted in 28 healthy male and female subjects. Group A received DMI 50 mg/day for 2 days followed by DMI 75 mg/day for the next 17 days. On Days 10-14, subjects also received 100 mg NFZ twice daily, and during Days 15-19, the NFZ dose was increased to 150 mg twice daily. Group B received 100 mg NFZ twice daily for 5 days followed by 150 mg NFZ twice daily for the next 14 days. On Days 11-12, subjects also received 50 mg DMI and during Days 13-19, the DMI dose was increased to 75 mg daily. Serial blood samples were collected for Group A and Group B. Plasma concentrations of NFZ and its metabolites, mCPP, hydroxynefazodone (OH-NFZ), and triazoledione, DMI, and the DMI metabolite, 2-hydroxydesipramine (2-OH-DMI) were determined. RESULTS Pharmacokinetic analysis demonstrated that the addition of NFZ to DMI did not result in any significant changes in the AUC(0-12), Cmax, or tmax of either DMI or 2-OH-DMI. Addition of DMI to NFZ resulted in statistically significant increases of 40% in the AUC(0-12) and 42% in the Cmax of mCPP. A significant decrease in the AUC(0-12) (19%) of OH-NFZ also was observed. The increase in mCPP may be attributable to inhibition of mCPP metabolism by DMI. CONCLUSION Overall, the combined administration of DMI and NFZ appeared to be safe and well tolerated in both treatment groups.