Chan R L, Henzl M R, LePage M E, LaFargue J, Nerenberg C A, Anik S, Chaplin M D
Department of Reproductive Medicine, Syntex Research, Palo Alto, CA 94304.
Clin Pharmacol Ther. 1988 Sep;44(3):275-82. doi: 10.1038/clpt.1988.150.
Nafarelin, a potent gonadotropin-releasing hormone (GnRH) agonist, was absorbed rapidly into systemic circulation (time to reach peak concentration, 20 to 40 minutes) after intranasal but not after sublingual or vaginal administration. Serum elimination half-life was about 2 hours. Nasal absorption of nafarelin was increased by increasing the concentration of the drug in the dose solution and incorporating sodium glycocholate into the nasal formulation. An optimal formulation providing maximum nasal absorption of nafarelin was one containing 1.75 mg nafarelin per ml and 2% sodium glycocholate. Bioavailability of this nasal formulation relative to a single subcutaneous dose averaged 21%. The metabolism and excretion of nafarelin were determined in three subjects after subcutaneous administration of [14C]-nafarelin. Radioactivity was excreted in approximately equal amounts in urine and stool. Six metabolites accounted for most of the radioactivity in urine. Four metabolites were short peptide fragments of nafarelin and the other metabolites were naphthylalanine and 2-naphthylacetic acid.
那法瑞林是一种强效促性腺激素释放激素（GnRH）激动剂，经鼻内给药后能迅速吸收进入体循环（达峰浓度时间为20至40分钟），但经舌下或阴道给药后则不然。血清消除半衰期约为2小时。通过增加剂量溶液中药物的浓度以及在鼻腔制剂中加入甘氨胆酸钠，那法瑞林的鼻腔吸收得以增强。提供那法瑞林最大鼻腔吸收的最佳制剂是每毫升含1.75毫克那法瑞林和2%甘氨胆酸钠的制剂。该鼻腔制剂相对于单次皮下给药的生物利用度平均为21%。在三名受试者皮下注射[14C] - 那法瑞林后，对那法瑞林的代谢和排泄情况进行了测定。放射性在尿液和粪便中的排泄量大致相等。六种代谢产物占尿液中大部分放射性。四种代谢产物是那法瑞林的短肽片段，其他代谢产物是萘丙氨酸和2 - 萘乙酸。
