Increased erythrocyte distribution of valproic acid in pharmacokinetic interaction with carbapenem antibiotics in rat and human.
Increased erythrocyte distribution of valproic acid in pharmacokinetic interaction with carbapenem antibiotics in rat and human.
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DOI：
10.1002/jps.20338
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发表时间：
2005-08
影响因子：
3.8
通讯作者：
K. Omoda;T. Murakami;R. Yumoto;J. Nagai;Y. Maeda;Yoshie Kiribayashi;M. Takano
中科院分区：
文献类型：
--
作者：
K. Omoda;T. Murakami;R. Yumoto;J. Nagai;Y. Maeda;Yoshie Kiribayashi;M. Takano
在临床药物治疗中，碳青霉烯类抗生素会与丙戊酸（VPA）发生药代动力学相互作用。在这里，我们从大鼠和人类中 VPA 的红细胞分布的角度研究了相互作用的机制。亚胺培南或帕尼培南静脉注射，然后VPA静脉注射或注入大鼠肠腔。亚胺培南和帕尼培南均显着降低血浆 VPA 水平。相反，这些抗生素不会影响或增加全血中的 VPA 水平，并增加体内 VPA 的红细胞分布。临床上有2例接受VPA治疗的患者因患有顽固性感染性疾病而静脉注射亚胺培南。在大鼠中观察到，亚胺培南使血浆 VPA 水平降低约 40%-60%，并增加 VPA 的红细胞分布。总之，VPA与碳青霉烯类抗生素之间的药代动力学相互作用，导致血浆VPA水平显着降低，部分原因可能是由于VPA红细胞分布增加。
Carbapenem antibiotics cause pharmacokinetic interaction with valproic acid (VPA) in clinical pharmacotherapy. Here, we investigated the mechanism of interaction from the viewpoint of erythrocyte distribution of VPA in rats and humans. Imipenem or panipenem was administered intravenously and then VPA intravenously or into the intestinal lumen in rats. Both imipenem and panipenem significantly decreased plasma VPA levels. In contrast, these antibiotics did not affect, or rather increased, VPA levels in whole blood, and increased the erythrocyte distribution of VPA in vivo. In clinical, two patients receiving VPA were given imipenem intravenously, because of intractable infectious diseases. Imipenem lowered plasma VPA levels by approximately 40%-60% of original levels, and increased the erythrocyte distribution of VPA, as observed in rats. In conclusion, the pharmacokinetic interaction between VPA and carbapenem antibiotics, in which plasma VPA levels were markedly reduced, may partly be derived from the increased erythrocyte distribution of VPA.