Ahr H J, Boberg M, Brendel E, Krause H P, Steinke W
Bayer AG, Wuppertal, Germany.
Arzneimittelforschung. 1997 Jun;47(6):734-45.
The absorption, distribution, metabolism, and excretion of miglitol ((2R,3R,4R,5S)-1-(2-hydroxyethyl)-2-(hydroxymethyl)-3,4,5-piperidinet riol, CAS 72432-03-2, BAY m 1099) have been studied following single and repeated administration of non-labelled and radiolabelled (3H, 14C) drug to rats, dogs, and human volunteers via different routes of administration (intravenous, oral, intraduodenal) and at various doses (0.3-450 mg/kg). After intravenous administration, miglitol is excreted rapidly and completely via the renal route. No indication was found for a metabolization of radiolabelled miglitol. The (renal) clearance of miglitol is in the range of the glomerular filtration rate. Miglitol is rapidly eliminated from plasma with apparent elimination half-lives of 0.4-1.8 h. Miglitol is virtually not bound to plasma proteins. After oral administration miglitol is rapidly and at low doses also completely absorbed. At higher doses (> or = 5 mg/kg in rats and dogs, > 50 mg in humans) a saturation of absorption becomes evident. Miglitol is distributed predominantly in the extracellular space. The volumes of distribution are low (0.3-0.8 l/ kg). In rats high concentrations were initially found in the kidneys, the blood and some well-perfused tissues. The permeation across the blood/brain barrier is very low. Elimination from organs and tissues occurs rapidly resulting in very low residual radioactivity in the body 2 days after dosing (< 0.9% of the dose). At this very low concentration level a terminal elimination phase of radioactivity characterized by half-lives of 50-110 h was observed giving rise to a slight tendency for accumulation (accumulation factors < 6) following repeated administration to rats. In pregnant rats [14C]miglitol crossed the placental barrier slowly and to a limited extent. In lactating rats miglitol was found in milk in concentrations similar to those in the maternal plasma.
已通过不同给药途径（静脉内、口服、十二指肠内）和各种剂量（0.3 - 450mg/kg）对大鼠、狗和人类志愿者单次及重复给予未标记和放射性标记（³H、¹⁴C）的米格列醇（(2R,3R,4R,5S)-1-(2 - 羟乙基)-2-(羟甲基)-3,4,5 - 哌啶三醇，CAS 72432 - 03 - 2，BAY m 1099），研究了其吸收、分布、代谢和排泄情况。静脉给药后，米格列醇通过肾脏途径迅速且完全排泄。未发现放射性标记的米格列醇有代谢迹象。米格列醇的（肾脏）清除率在肾小球滤过率范围内。米格列醇从血浆中迅速消除，表观消除半衰期为0.4 - 1.8小时。米格列醇几乎不与血浆蛋白结合。口服给药后，米格列醇迅速吸收，低剂量时也完全吸收。在较高剂量时（大鼠和狗中≥5mg/kg，人类中＞50mg），吸收饱和变得明显。米格列醇主要分布在细胞外空间。分布容积较低（0.3 - 0.8l/kg）。在大鼠中，最初在肾脏、血液和一些灌注良好的组织中发现高浓度。穿过血脑屏障的渗透率非常低。给药2天后，器官和组织中的消除迅速，导致体内残留放射性非常低（＜剂量的0.9%）。在这个非常低的浓度水平下，观察到放射性的终末消除相，半衰期为50 - 110小时，对大鼠重复给药后有轻微的蓄积倾向（蓄积因子＜6）。在怀孕大鼠中，[¹⁴C]米格列醇缓慢且有限地穿过胎盘屏障。在哺乳期大鼠的乳汁中发现米格列醇，其浓度与母体血浆中的浓度相似。
