Illing H P, Ings R M, Johnson K I, Fromson J M
Xenobiotica. 1983 Jul;13(7):439-49. doi: 10.3109/00498258309052282.
The disposition of 14C-loprazolam has been studied in rat, dog, cynomolgus monkey and man using oral and parenteral dosing. In all species 14C was excreted principally in the faeces irrespective of the route of administration. In surgically prepared animals, 46% dose (rat) or 60% (dog) was excreted in bile and, together with urinary excretion, indicates that approx. two-thirds of an oral dose was absorbed. In rat there was relatively little enterohepatic circulation (approximately 26%) compared to dog (approximately 73%). Whole-body autoradiography and tissue-distribution studies in rat showed that 14C was distributed principally in liver and intestine, and was eliminated within 24 h. 14C was found in brain of rat and dog; in dog concn. levels were higher in white matter than in grey matter. In studies using pigmented animals, 14C was associated with the uveal tract of the eye and with other melanin-containing tissues. This was reversible and was eliminated from the eye of rat with a half-life of 3.4 d. Blood and plasma concn. of 14C and of unchanged loprazolam declined relatively rapidly in rat. In dog, cynomolgus monkey and man, total 14C concn. in blood fell more slowly than unchanged loprazolam. Less than 85% of loprazolam was protein bound in rat, dog or human plasma in vitro.
已通过口服和肠胃外给药，在大鼠、狗、食蟹猴和人类中研究了14C-氯普拉唑仑的处置情况。在所有物种中，无论给药途径如何，14C主要通过粪便排泄。在手术制备的动物中，46%的剂量（大鼠）或60%（狗）通过胆汁排泄，加上尿液排泄，表明约三分之二的口服剂量被吸收。与狗（约73%）相比，大鼠的肠肝循环相对较少（约26%）。大鼠的全身放射自显影和组织分布研究表明，14C主要分布在肝脏和肠道，并在24小时内消除。在大鼠和狗的脑中发现了14C；在狗中，白质中的浓度水平高于灰质。在使用有色动物的研究中，14C与眼睛的葡萄膜和其他含黑色素的组织有关。这是可逆的，在大鼠眼中的消除半衰期为3.4天。大鼠血液和血浆中14C和未变化的氯普拉唑仑浓度相对迅速下降。在狗、食蟹猴和人类中，血液中总14C浓度下降的速度比未变化的氯普拉唑仑慢。在体外，大鼠、狗或人血浆中与蛋白质结合的氯普拉唑仑不到85%。
