Coadministration of nefazodone and desipramine: a pharmacokinetic interaction study.

Author(s): Khan AY, Preskorn SH, Horst WD

Affiliation(s): University of Kansas School of Medicine-Wichita, Department of Psychiatry & Behavioral Sciences, 1010 North Kansas Street, Wichita, KS 67214, USA.

Publication date & source: 2007-05, J Pak Med Assoc., 57(5):230-5.

Publication type: Clinical Trial

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.