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.
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 26 d with either oral drug. On day 27, a tolerance test was used to determine whether these agents interfered with vitamin absorption. During the first 8 d, 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.
Schindler
Rainer
R
Department of Human Nutrition and Food Science, Christian-Albrechts-University zu Kiel, D-24 116, Germany. rschindler@nutrfoodsc.uni-kiel.de
Fielenbach
Tanja
T
Rave
Gerhard
G
D000042:Absorption; D000284:Administration, Oral; D000638:Amiodarone / Q000009:adverse effects*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects*; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001682:Biological Availability; D001835:Body Weight; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D013997:Time Factors; D014291:Trimeprazine / Q000009:adverse effects*; D014801:Vitamin A / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*
D000889:Anti-Arrhythmia Agents; D014150:Antipsychotic Agents; D004791:Enzyme Inhibitors; D014801:Vitamin A; D014291:Trimeprazine; D002265:Carboxylic Ester Hydrolases; C022523:retinyl esterase; D000638:Amiodarone