Igarashi T, Yamamoto M, Yamada M, Ogata E, Katsuragi S
Pharmatherapeutica. 1982;3(2):79-85.
1-34 human parathyroid hormone (1-34 hPTH) was synthesized by a liquid-phase method and prepared for clinical use (specific activity, 3281 U/mg). With this preparation, the toxicity was studied in 22 normal volunteers and the metabolic effects in 15 individuals. Intradermal administration of 4 ng of 1-34 hPTH caused neither abnormal local skin reactions nor toxicity in terms of subjective and objective parameters. When administered intravenously at doses of from 2 to 20 microgram as a bolus, the preparation caused no acute or subacute toxicity judging from the results of various clinical and laboratory studies, except for transient mild hypotension and headache in a minority of subjects. For diagnostic use, 20 microgram of 1-34 hPTH administered intravenously was found to produce effects almost equivalent to those of 200 USPU U of Parathormone (PTE, Eli Lilly). Thus, the criteria for differentiation of hypoparathyroidism from pseudo-hypoparathyroidism devised with 2000 USP U of PTE as a test substance was found to be applicable when 20 microgram of 1-34 hPTH was utilized.
采用液相法合成了1-34人甲状旁腺激素(1-34 hPTH)并制备用于临床(比活性为3281 U/mg)。使用该制剂,在22名正常志愿者中研究了其毒性,并在15名个体中研究了其代谢效应。皮内注射4 ng的1-34 hPTH,无论从主观还是客观参数来看,均未引起局部皮肤异常反应或毒性。当以2至20微克的剂量静脉推注给药时,根据各种临床和实验室研究结果,该制剂未引起急性或亚急性毒性,少数受试者出现短暂轻度低血压和头痛除外。用于诊断时,发现静脉注射20微克的1-34 hPTH产生的效果几乎等同于200美国药典单位(USP U)的甲状旁腺素(PTE,礼来公司)。因此,发现以2000 USP U的PTE作为测试物质制定的鉴别甲状旁腺功能减退和假性甲状旁腺功能减退的标准,在使用20微克的1-34 hPTH时同样适用。