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  • Title: [Pharmacokinetics of enalapril and metoprolol in hypertensive patients with hepatic pathology].
    Author: Lazebnik LB, Mikheeva OM, Drozdov VN, Petrakov AV, Sil'vestrova SIu.
    Journal: Ter Arkh; 2007; 79(9):18-25. PubMed ID: 18038581.
    Abstract:
    AIM: To examine characteristics of pharmacokinetics and pharmacodynamics of enalapril and metoprolol in hypertensive patients with gastrointestinal diseases to make relevant corrections in the treatment. MATERIAL AND METHODS: The study included 36 hypertensive patients with steatosis, hepatic cirrhosis and ulcer. All the patients received metoprolol or enalapril. Concentrations of metoprolol and enalaprilate (active enalapril metabolite) were determined with high performace liquid chromatography. The findings gave grounds for calculation of mean drug retention time (MRT) and area under curve "concentration-time" (AUC). Efficacy of the drugs was estimated by the data of 24-h blood pressure monitoring. RESULTS: Hypertensive patients with hepatic diseases given enalapril exhibited lowering of maximal concentration (C(max)) of enalaprilate and prolongation of time of its reaching (T(max)) compared to ulcer patients. MRT and AUC were increased in hepatic cirrhosis patients treated with enalapril and metoprolol. Metoprolol C(max) in this group of patients was higher than in the controls. Blood pressure monitoring showed that enalapril therapy was more effective in ulcer patients vs patients with liver diseases. Metoprolol treatment of hypertensive patients with hepatic cirrhosis resulted in development of bradycardia. CONCLUSION: In hypertensive patients with liver diseases on enalapril therapy its metabolite production may appear insufficient for therapeutic effect and higher dose may be needed. Metoprolol in the treatment of hypertensive patients with hepatic cirrhosis should be used with caution because of disturbance of its metabolism and possible cumulative effects.
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