(±)‐1‐〔4‐〔2‐(Cyclopropylmethoxy)ethyl〕phenoxy〕‐3‐isopropylamino‐2‐propanol hydrochloride(Betaxolol hydrochloride)の体内動態 (第2報): ラットにおける反復投与時の血中濃度推移,分布,代謝,排せつ,蓄積性および肝薬物代謝酵素系に対する影響  [in Japanese] Studies on the metabolic fate of (.+-.)-1-(4-(2-(cyclopropylmethoxy)ethyl)phenoxy)-3-isopropylamino-2-propanol hydrochloride (betaxolol hydrochloride). (2): Blood level profiles, distribution, metabolism, excretion, aecumulation and effects on the hepatic drug-metabolizing enzyme activities of betaxolol after repeated oral administration to rats.  [in Japanese]

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Abstract

<SUP>14</SUP>Cで標識したBetaxololまたは非標識Betaxololを,ラットに1日1回最大21日間反復経口投与(5mg/kg/day)し,反復投与時の体内動態および肝ミクロゾーム薬物代謝酵素活性への影響について検討した.<BR>1.<SUP>14</SUP>C-Betaxolo1を21日間反復投与したとき,投与後2hrの血液中放射能濃度は,初回投与以降ほぼ一定で推移した.投与後24hrの血液中放射能濃度は投与開始後徐々に増加し,14回投与以降ほぼ一定で推移した.反復投与後の血液中放射能濃度の減少は,単回投与時に比べて遅延傾向を示したが,14回投与と21回投与後の血液中放射能濃度推移はほとんど同じであった.<BR>2.反復投与期間中,尿および糞中への放射能の累積排泄率はほぼ一定の割合で増加した.最終投与後24hrまでの総投与量に対する排泄率は,尿中に80.0%,糞中に18.8%であり,最:終投与後168hrまでに総投与量の98.9%が排泄された.<BR>3.反復投与後24hrの組織中放射能濃度は,7日目または14日目まで徐々に上昇し,その後ほぼ一定の値で推移した.21日間反復投与後の組織中放射能濃度は経時的に減少した.<BR>4.反復投与後の血漿,臓器(肝臓腎臓,心臓)および尿中放射能に対する未変化体および代謝物の割合は,いずれも単回投与後のそれと類似した.<BR>5.反復投与により肝ミクロゾーム薬物代謝酵素系にほとんど影響を与えなかった.

The absorption, distribution, metabolism, excretion and accumulation of Betaxolol were investigated after repeated oral administration of <SUP>14</SUP>C-Betaxolol (5mg/kg/day) to male rats for 21 days. The effect of Betaxolol on the hepatic drug-metabolizing enzyme activities was also investigated after repeated oral administration of Betaxolol (5 and 20mg/kg/day) to male rats for 21 days.<BR>1. Blood levels of radioactivity at 2hr after each dosing remained almost constant since the 1st day. During the repeated oral administration of <SUP>14</SUP>C-Betaxolol, blood levels of radioactivity at 24hr after each dosing continued to increase till the 14th day. After the 14th administration, blood levels of radioactivity reached to the plateau. Blood levels of radioactivity after repeated oral administration decreased more slowly than that after a single administration.<BR>2. The excretion rates of radioactivity in the urine and feces were nearly constant during the period of repeated administration of <SUP>14</SUP>C-Betaxolol, and were similar to those after a single administration. Within 24hr after the last dosing, 80% of the administered radioactivity was recovered in urine and 18.8% in feces.<BR>3. The tissue levels of radioactivity at 24hr after each dosing increased gradually until the 14th administration, followed by remaining of almost same level. The tissue levels of radioactivity after 21 days repeated administration decreased gradually.<BR>4. The percentages of unchanged Betaxolol and metabolites to radioactivity in plasma, tissues (liver, kidney and heart) and urine after repeated administration were almost same as those after a single administration.<BR>5. Betaxolol had no effect on the hepatic drug-metabolizing enzyme system.

Journal

  • Drug Metabolism and Pharmacokinetics

    Drug Metabolism and Pharmacokinetics 5(5), 699-710, 1990

    The Japanese Society for the Study of Xenobiotics

Codes

  • NII Article ID (NAID)
    130004878689
  • Text Lang
    JPN
  • ISSN
    0916-1139
  • Data Source
    J-STAGE 
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