The deleterious effect of Bordetella pertussis vaccine and poly(rI.rC) on the metabolism and disposition of phenytoin.
The deleterious effect of Bordetella pertussis vaccine and poly(rI.rC) on the metabolism and disposition of phenytoin.
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百日咳博德特氏菌疫苗和聚（rI.rC）对苯妥英代谢和处置的有害影响。
DOI：
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发表时间：
1979
影响因子：
3.5
通讯作者：
K. Renton
中科院分区：
文献类型：
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作者：
K. Renton
用百日咳波氏杆菌疫苗或合成多核苷酸聚(rI.rc.)预先处理24小时的大鼠，血液中苯妥英的排除量显著减少。苯妥英的半衰期在两种药物中都增加了约4倍。经百日咳杆菌菌苗或聚rI.rC处理的大鼠微粒体中，苯妥英钠的体外羟化水平分别下降了36%和53%。在正常的微粒体悬液中加入这些药物对苯妥英羟化没有影响，表明生物转化率的降低不是由于直接的酶抑制。百日咳菌苗或聚(rI.rC)处理的大鼠肝脏内质网细胞色素P-450水平降低，苯妥英羟化程度和清除率降低。
The elimination of phenytoin from blood was significantly decreased in rats pretreated 24 hr previously with Bordetella pertussis vaccine or the synthetic polynucleotide poly(rI.rC.). Phenytoin half-life was increased about 4-fold by both agents. In microsomes prepared from rats pretreated with B. pertussis vaccine or poly(rI.rC) the hydroxylation of phenytoin in vitro was decreased by 36 nad 53%, respectively. The addition of these agents to normal microsomal suspensions had no effect on phenytoin hydroxylation, demonstrating that the decrease in biotransformation was not due to direct enzyme inhibition. The decrease in phenytoin hydroxylation and elimination rate resulted from depressed levels of cytochrome P-450 in the hepatic endoplasmic reticulum of rats treated with B. pertussis vaccine or poly(rI.rC).