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YAKUGAKU ZASSHI 125(2) 197\203 (2005) Ý 2005 The Pharmaceutical Society of Japan

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Simple Method for Precognition of Drug Interaction between Oral Iron and
Phenolic Hydroxyl Group­containing Drugs
Nobuyoshi SUNAGANE,Þ,a Etsuko YOSHINOBU,a Nobuko MURAYAMA,a Yasufumi TERAWAKI,b
Naoki KAMIMURA,c and Tsutomu URUNOa
Faculty of Pharmaceutical Sciences, Tokyo University of Science (RIKADAI),a 2641 Yamazaki, Noda City 278_8510,
Japan, Kirishima Citizens' Pharmacy,b 3_22_17 Chuo, Kirishima City 899_
4332, Japan, and
Fujimidai Pharmacy,c 2_18_7 Fujimidai, Kunitachi City 186_0003, Japan
(Received September 10, 2004; Accepted November 10, 2004)
In the present study, we devised a simple method for detecting the drug interaction between oral iron preparations
and phenolic hydroxyl group­containing drugs, using the coloring reaction as indicator, due to the formation of com­
plexes 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 puriˆed water to make sample suspensions for testing. Thirty minutes after mixing an oral iron sus­
pension 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 classiˆed 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
signiˆcant 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 prepa­
ration showed no in‰uence 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 group­containing drugs, and the drugs with a higher grade in screening may in­
duce drug interactions with oral iron.
Key words\\drug interaction; oral iron; phenolic drug; levodopa; droxidopa

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Droxidopa Preparation (B) or Acetaminophen Prepa­ ration (C) Left: oral iron suspension. Fig. middle: mixed suspension. 2. 1 Éᦵ½ªCeg‰TCNŠ“ntyу ðSÜntƬ‡·éƼ¿É°˜ÈF²Ï»ð­ »µC{XNŠ[j“OÌî€ÅÍOŒ[h 3 É» è³ê½D ªq†ÉtFm[‹«…_îðÜL·éãòiÅ oûpÜƵÄp¢çêéàÌ̤¿CÕ°ãÉp ³êéÆl¦çê½ 14 íÌãòiÉ¢ÄÈÕX NŠ[j“OðsÁ½DSÜƵÄNG“_æêS igŠE€itF~Ajðp¢½Æ«Ì‹Êð Table 1 ÉvñµÄ¦µ½Dí±ãòi̤¿A‚ LVVŠ“C°_T‹u^‚[‹C°_e‹u^Š “Ì 3 íÈOÍC»ÌöxÉ·ÍFßçêéàÌÌ Fig. . right: tetracycline suspension (A) or tea (B). Coloring Reaction after Mixing Oral Iron (Sodium Ferrous Citrate) Preparation with Tetracycline (Demethyl­ chlortetracycline Hydrochloride) Preparation (A) or Tea (B) Left: oral iron suspension. 1. right: test drug suspension. 125 (2005) Fig.200 Vol. middle: mixed suspension. Coloring Reaction after Mixing Oral Iron (Sodium Ferrous Citrate) Preparation with Levodopa Preparation (A).

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