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A comparative study on the effects of oral amiodarone and trimeprazine, two in vitro retinyl ester hydrolase inhibitors, on the metabolic availability of vitamin A in rats

Published online by Cambridge University Press:  08 March 2007

Rainer Schindler ,
Tanja Fielenbach  and
Gerhard Rave
Rainer Schindler*
Affiliation:
Department of Human Nutrition and Food Science, Christian-Albrechts-University zu Kiel, D-24 116, Germany
Tanja Fielenbach
Affiliation:
Department of Human Nutrition and Food Science, Christian-Albrechts-University zu Kiel, D-24 116, Germany
Gerhard Rave
Affiliation:
Institute for Variationsstatistik, Christian-Albrechts-University zu Kiel, D-24 116, Germany
*
*Corresponding author: Dr R. Schindler, fax +49 431 880 5679, email [email protected]
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Abstract

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Amiodarone, an antiarrhythmic drug, and trimeprazine, an antipsychotic drug, are both in vitro inhibitors of retinyl ester hydrolase. To determine whether these agents have deleterious effects on aspects of vitamin A metabolism, Brown Norway rats (n 18) were treated at clinically equivalent doses once daily for 26d with either oral drug. On day 27, a tolerance test was used to determine whether these agents interfered with vitamin absorption. During the first 8d, the plasma retinol level declined in all animals. Between days 12 and 27, it rose to near pre-treatment concentrations in the control and trimeprazine groups and remained relatively constant at low levels (P<0·001) in the amiodarone group. The intestinal absorption of vitamin A was reduced (P<0·05) in the amiodarone group compared with the placebo and trimeprazine groups, which did not differ significantly from each other. At the end of the 4-week treatment period, hepatic retinyl ester hydrolase activity was lower in the drug-dosed rats (P=0·06 for amiodarone) than in the controls. With regard to effects on liver reserves, drug treatment resulted in vitamin A depletion (P<0·019), and distinctive patterns of retinol and its esters were seen in response to dosing. In conclusion, amiodarone and trimeprazine have been shown to influence different aspects of retinoid metabolism, namely absorption, storage and transport. In clinical practice, the routine unmonitored use of these drugs and the suggestion that these agents be taken with meals are not recommended.

Keywords

Amiodarone–vitamin A interactionTrimeprazine–vitamin A interactionRetinyl ester hydrolase
Type
Research Article
Information
British Journal of Nutrition , Volume 94 , Issue 5 , November 2005 , pp. 675 - 683
Copyright
Copyright © The Nutrition Society 2005

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