MECHANISM OF ENHANCED DRUG EFFECTS PRODUCED BY DILUTION OF ORAL DOSE
MECHANISM OF ENHANCED DRUG EFFECTS PRODUCED BY DILUTION OF ORAL DOSE
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DOI：
10.1016/0041-008x(71)90103-7
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发表时间：
1971-01-01
影响因子：
3.8
通讯作者：
MIYA, TS
中科院分区：
文献类型：
--
作者：
BOROWITZ, JL;MOORE, PF;MIYA, TS
弱酸性或弱碱性的药物和水溶性有限的药物在稀释溶液或混悬液中口服给药时毒性更大。大鼠口服戊巴比妥钠（50 mg/kg）后，以稀溶液（5 ml/100 g体重）给药后的睡眠起效快于以浓溶液（0.5 ml/100 g体重）给药后的睡眠起效。然而，口服水（5 ml/100 g体重）不会影响氨基比林的ip毒性。大鼠口服稀溶液（0.8%）后水杨酸钠血浆浓度显著高于口服浓溶液（25%）。这些数据表明，口服稀释溶液比浓缩溶液更快地吸收到体循环中。低浓度药物的毒性增加现象似乎涉及两种机制：（1）快速胃排空和（2）暴露于相对较大液体体积中口服给药的药物溶液的较大吸收表面。
Drugs which are weak acids or weak bases and drugs with limited water solubility are more toxic by the oral route when given in dilute solution or suspension. The onset of sleep after po administration of sodium pentobarbital (50 mg/kg) is faster in rats when the drug is given in dilute solution (5 ml/100 g body wt) than when it is given in concentrated solution (0.5 ml/100 g body wt). However, administration of water po (5 ml/100 g body wt) does not affect the ip toxicity of aminopyrine. Sodium salicylate plasma levels are significantly higher in rats after the drug is given po in dilute (0.8%) solution than when it is given po in concentrated (25%) solution. These data indicate that drugs are absorbed more rapidly into the systemic circulation when given po in dilute rather than concentrated solution. Two mechanisms appear to be involved in the increased toxicity phenomenon with low concentrations of drugs: (1) rapid stomach emptying and (2) exposure to a large absorptive surface of drug solutions given po in a relatively large fluid volume.