Swart P J, De Zeeuw R A
Department of Analytical Chemistry and Toxicology, University Centre for Pharmacy, Groningen, The Netherlands.
Pharmazie. 1992 Aug;47(8):613-5.
The absorption of the dopamine D2 agonist S(-)-2-(N-propyl-N-2-thienylethylamino)-5-hydroxy-tetralin hydrochloride (1; N-0923) was studied in fasted and non-fasted male Albino Wistar rats after intragastric administration of 10.0 mumol.kg-1. Blood samples up to 120 min were obtained from the portal vein and the levels of 1 were monitored with a sensitive HPLC method. The maximal fraction of the drug reaching the liver invariable was less than 1% of the dose. Maximal plasma levels of 30 pmol.ml-1 were found within 12 min after dosing in fasted animals. Plasma concentrations of 1 were measurable up to 60 min, after which they were below the quantitation limit of the assay (10 pmol.ml-1). This did not allow detailed kinetic analysis. Analysis of the portal blood samples obtained after an oral dosing of 10.0 mumol.kg(-1)1 spiked with 0.37 MBq tritium labelled drug showed that the amount of unchanged drug which reaches the liver invariably was comparable with the concentrations found in the study without radioactivity. In vitro incubation of 1 with gastric juice and gut contents showed no degradation. Therefore, it can be concluded that 1 undergoes an extensive metabolism in the gastrointestinal mucosa.
在禁食和非禁食的雄性白化Wistar大鼠中，以10.0 μmol·kg⁻¹的剂量灌胃给药后，研究了多巴胺D2激动剂S(-)-2-(N-丙基-N-2-噻吩基乙氨基)-5-羟基四氢萘盐酸盐（1；N-0923）的吸收情况。在给药后120分钟内，从门静脉采集血样，并用灵敏的高效液相色谱法监测1的水平。到达肝脏的药物最大比例始终小于给药剂量的1%。禁食动物给药后12分钟内，血浆中药物最大浓度达到30 pmol·ml⁻¹。给药后60分钟内可检测到血浆中1的浓度，之后低于检测方法的定量限（10 pmol·ml⁻¹）。这使得无法进行详细的动力学分析。对口服10.0 μmol·kg⁻¹ 1并加入0.37 MBq氚标记药物后采集的门静脉血样分析表明，到达肝脏的未变化药物量始终与未进行放射性研究中发现的浓度相当。1与胃液和肠内容物的体外孵育未显示出降解。因此，可以得出结论，1在胃肠道黏膜中经历了广泛的代谢。
