Pharmacokinetics and disposition of 4′-O-tetrahydropyranyladriamycin in mice by HPLC analysis
Pharmacokinetics and disposition of 4′-O-tetrahydropyranyladriamycin in mice by HPLC analysis
复制标题
HPLC 分析 4-O-四氢吡喃霉素在小鼠体内的药代动力学和分布
DOI：
10.1007/bf00257523
复制
发表时间：
2004
影响因子：
3
通讯作者：
H. Umezawa
中科院分区：
文献类型：
--
作者：
H. Iguchi;H. Tone;T. Ishikura;T. Takeuchi;H. Umezawa
小鼠静脉注射4′-O-四氢吡喃阿霉素（4 ′-O-tetrahydropyranyladriamycin，THP）后血浆浓度迅速下降，t1/2（α）为0.453min，注射5 mg/kg后2 min仅检测到1.2 μg/ml THP。药物立即转移到各种组织，其中药物水平远高于血浆浓度。给药后2 h，肺和脾中THP含量分别为8.26和13.6 μg/g。THP的主要代谢产物为13-二氢THP、ADM、7-脱氧阿霉素酮和7-脱氧-13-二氢阿霉素酮。根据HPLC荧光光谱分析，注射后48小时，仅1.12%的剂量以THP及其代谢产物的形式在尿液中回收。观察到的处置THP与阿霉素（ADM）进行了比较。THP在血浆中的消失和组织转移均快于ADM，脾、肺组织中THP浓度高于相应ADM浓度，而心、肝组织中THP浓度低于相应ADM浓度。药物浓度下降更快，在大多数组织中的情况下，THP比ADM。组织分布后，单次推注和多次注射进行了比较和讨论。
The plasma level of 4′-O-tetrahydropyranyladriamycin (THP) declined rapidly after IV injection to mice, with a t1/2(α) of 0.453 min. Only 1.2 μg/ml THP was detected 2 min after injection of 5 mg/kg. The drug was immediately transferred to various tissues, where the drug levels were much higher than the plasma concentration. In the lung and spleen, 8.26 and 13.6 μg/g THP was present, respectively, 2 h after administration. Major metabolites of THP were 13-dihydro-THP, ADM, 7-deoxyadriamycinone, and 7-deoxy-13-dihydro-adriamycinone. Only 1.12% of the dose had been recovered in the urine by 48 h after injection as THP and its metabolites, according to analysis by HPLC fluorospectroscopy. The observed disposition of THP was compared with that of adriamycin (ADM). The plasma disappearance and tissue transfer of THP were faster than those of ADM. THP levels in the spleen and lung were higher and those in the heart and liver were lower than the corresponding ADM levels. Drug levels declined more quickly in most tissues in the case of THP than of ADM. Tissue distributions after single bolus and multiple injections were also compared and discussed.