Abstract
Desipramine (DMI), a metabolite of imipramine (IP), has approximately the same antidepressant activity as the mother compound. It is important to clarify the fractional ratio of metabolism from IP to DMI (fmIP-DMI). We have developed a new technique to estimate fmIP-DMI by the use of a co-administration technique. After co-administration of a mixture of IP-d4 and DMI-d0 to rats, area under the plasma concentration-time curve (AUC) and renal excretion of DMI-d4 and DMI-d0 were examined. fmIP-DI estimated from the ratio of AUC of DMI-d4 to that of DMI-d0 was almost the same as fmIP-DMI calculated from the ratio of the amount of excreted DMI-d4 to that of DMI-d0. This means that fmIP-DMI can be calculated by using the renal excretion data instead of AUC. The relationship between fmIP-DMI and IP-d4 dose is also discussed.
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