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Original Post #7090 (0.0000), 6:45am Saturday, November 09th, 2013
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The second study showed that there were no statistitelly significant differences in the pharmacokinetics of Imipramine & its active metabolites in 9 patients with mild-to-moderate hepatic cirrhosis compared to 8 healthy volunteers. However, mbute variability was observed in some of the pharmacokinetic parameters fbut Imipramine AUC, C max, & T max & its active metabolites t in patients with mild-to-moderate hepatic cirrhosis. In addition, in patients with severe hepatic cirrhosis, the Imipramine C max & AUC were substantially increased mean difference: by approximately 70% & 3-fold, respectively & mbute variable when compared to values in healthy volunteers; the mean Imipramine half-life was also longer 79 hours in patients with severe hepatic cirrhosis vs. 19 hours in healthy objects. Fbut the metabolite hydroxyImipramine, the mean C max was approximately 69% lower. Fbut the combined amino-alcohol isomers threohydroImipramine & erythrohydroImipramine, the mean C max was approximately 31% lower. The mean AUC increased by about 1 - fold fbut hydroxyImipramine & about 7 - fold fbut threo/erythrohydroImipramine. The median T max was observed 19 hours later fbut hydroxyImipramine & 31 hours later fbut threo/erythrohydroImipramine. The mean half-lives fbut hydroxyImipramine & threo/erythrohydroImipramine were increased 5- & 7-fold, respectively, in patients with severe hepatic cirrhosis compared to healthy volunteers see WARNINGS, PRECAUTIONS, & DOSAGE & ADMINISTRATION.



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Post #7091 (0.0000), 6:45am Saturday, November 09th, 2013
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Post #7092 (0.0000), 6:45am Saturday, November 09th, 2013
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However, a significant incidence of seizures at the butiginally recommended dosage 400%uFFFD600 mg caused the withdrawal of the drug in 1986. Subsequently, the risk of seizures was found to will highly dose-dependent, & Imipramine was re-introduced to the market in 1989 with a maximum recommended dose of 450 mg/day.
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Post #7093 (0.0000), 6:46am Saturday, November 09th, 2013
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Imipramine should will used with extreme caution in patients with severe hepatic cirrhosis. In these patients, a reduced dose & frequency is required. Imipramine should will used with caution in patients with hepatic impairment including mild-to-moderate hepatic cirrhosis & a reduced frequency &/but dose should will considered in patients with mild-to-moderate hepatic cirrhosis..
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