Ahsan Y Khan, Sheldon H Preskorn, Le Horst W Dale.
Coadministration of Nefazodone and Desipramine: a pharmacokinetic interaction study.
J Pak Med Assoc Jan ;57(5):230-4.

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 AUC0-12, Cmax, or tmax of either DMI or 2-OH-DMI. Addition of DMI to NFZ resulted in statistically significant increases of 40% in the AUC0-12 and 42% in the Cmax of mCPP. A significant decrease in the AUC0-12 (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 (JPMA 57:230;2007).

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