Measurement of the Fractional Ratio of Demethylation of Imipramine in Rat by Using a Co-administration Technique

概要

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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 (fm^<IP-DMI>). We have developed a new technique to estimate fm^<IP-DMI> by the use of a co-administration technique. After co-administration of a mixture of IP-d_4 and DMI-d_0 to rats, area under the plasma concentration-time curve (AUC) and renal excretion of DMI-d_4 and DMI-d_0 were examined. fm^<IP-DI> estimated from the ratio of AUC of DMI-d_4 to that of DMI-d_0 was almost the same as fm^<IP-DMI> calculated from the ratio of the amount of excreted DMI-d_4 to that of DMI-d_0. This means that fm^<IP-DMI> can be calculated by using the renal excretion data instead of AUC. The relationship between fm^<IP-DMI> and IP-d_4 dose is also discussed.
社団法人日本薬学会の論文
1988-08-25