[Simple method for precognition of drug interaction between oral iron and phenolic hydroxyl group-containing drugs].
In the present study, we devised a simple method for detecting the drug interaction between oral iron preparations and phenolic hydroxyl group-containing drugs, using the coloring reaction as indicator, due to the formation of complexes or chelates. In the method, oral iron preparations and test drugs in amounts as much as single dose for adults were added to 10 ml of purified water to make sample suspensions for testing. Thirty minutes after mixing an oral iron suspension and a test drug suspension, the change of color in the mixture was observed macroscopically and graded as 0 to 3, with a marked color change judged as grade 3 and no color change as grade 0. Screening of 14 test drugs commonly used orally was carried out. When using sodium ferrous citrate preparations as oral iron, 5 were classified as grade 3, 2 as grade 2, 4 as grade 1, and 3 as grade 0, respectively. To verify usefulness of the method, the interactions suggested by screening were pharmacokinetically assessed by measuring serum concentrations of the drug in mice. When a levodopa or droxidopa preparation, judged as grade 3 in screening, was concomitantly administered with an iron preparation, a significant reduction in bioavailability of the test drug was observed, indicating possible drug interaction between the test drug and oral iron. Combined administration of an acetaminophen preparation, judged as grade 1, and oral iron preparation showed no influence on the bioavailability of the test drug, implying no detectable interactions between them. In conclusion, the simple method devised in the present study is useful for precognition of drug interactions between oral iron preparations and phenolic hydroxyl group-containing drugs, and the drugs with a higher grade in screening may induce drug interactions with oral iron.
Sunagane
Nobuyoshi
N
Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda City 278-8510, Japan. sunagane@rs.noda.tus.ac.jp
Yoshinobu
Etsuko
E
Murayama
Nobuko
N
Terawaki
Yasufumi
Y
Kamimura
Naoki
N
Uruno
Tsutomu
T
D000082:Acetaminophen / Q000493:pharmacokinetics; D000818:Animals; D001682:Biological Availability; D001702:Biopharmaceutics / Q000379:methods*; D019343:Citric Acid; D003124:Colorimetry / Q000379:methods; D015103:Droxidopa / Q000493:pharmacokinetics; D004347:Drug Interactions; D005296:Ferrous Compounds / Q000493:pharmacokinetics; D058085:Iron Compounds / Q000493:pharmacokinetics; D007980:Levodopa / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013535:Suspensions
D005296:Ferrous Compounds; D058085:Iron Compounds; D013535:Suspensions; D019343:Citric Acid; C016600:ferrous citrate; D000082:Acetaminophen; D007980:Levodopa; D015103:Droxidopa