Reduced drug elimination in congestive heart failure: Studies using aminopyrine as a model drug |
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Authors: | Gershon W Hepner Elliot S Vesell Kermit R Tantum |
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Institution: | Torrance, California, USA;Hershey, Pennsylvania, USA |
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Abstract: | Aminopyrine disposition was studied in 11 patients with congestive heart failure (CHF) and 15 control patients. The aminopyrine metabolic clearance rate was 29.7 ± 7.1 ml/min (mean ± SEM) in the patients with CHF and 125.1 ± 5.7 ml/min (mean ± SEM) in the control patients (p < 0.01). The aminopyrine breath test was 2.6 ± 0.4 per cent (mean ± SEM) in the patients with CHF and 5.6 ± 0.3 per cent (mean ± SEM) in the control subjects (p < 0.01). Probably due to fluid retention in CHF, the apparent volume of distribution of aminopyrine increased to 63.3 ± 4.9 liters (mean ± SEM) in patients with CHF from 43.1 ± 1.9 liters (mean ± SEM) in control patients, thereby further impairing aminopyrine elimination in patients with CHF (p < 0.01). The aminopyrine breath test was measured in a group of eight patients before treatment for an acute episode of CHF and seven to 10 days after initiation of therapy: in each patient clinical improvement was associated with an increased aminopyrine breath test, mean values of aminopyrine breath test increasing from 2.8 per cent before treatment to 5.2 per cent after initiation of treatment (p < 0.01). These results suggest that in patients with CHF hepatic drug-metabolizing activity is impaired, and the volume of distribution of drugs is increased, with consequent retardation in rates of drug elimination. |
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Keywords: | Requests for reprints should be addressed to Dr Elliot S Vesell Department of Pharmacology The Pennsylvania State University Hershey Pennsylvania 17033 |
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