Nagatomi H, Mitsuhiro S, Ogita T, Mizushima Y
Nihon Yakurigaku Zasshi. 1981 Aug;78(2):109-15.
The absorption of and specific antibody formation to Artroglobina (:AG, beta and gamma-globulin fractions of anticartilage-antiparathyroid immune serum from the horse) administered into the rectum were studied in rats and guinea-pigs, an immunological tests in the "Phase I Study" were carried out using serum from volunteers. 1) When the radio-labelled AG (125I-AG) was administered into the rat rectum, the plasma level of 125I reached the maximum (3.1% of the total dosage) at 2 hour later and 0.3 per cent of the total dosage retained the reactivity with the anti-Fab antibody. 2) Gel diffusion and PCA tests gave positive reactions in the sera after the second administration of AG in a dose of 20 mg/kg, corresponding to 40 times the clinical dose, with a certain interval after the first treatment. From the results, it was confirmed that rectally-administered AG induces mainly IgG or IgE antibody formation, in the rat. 3) The administration of AG through the rectum did not induce the systemic anaphylaxic reaction in the guinea-pigs which had been administered AG into the rectum. The intravenous challenge, however, resulted in a positive anaphylaxic reaction in animals treated with AG rectally. This indicates the sensitization of the animal with AG by the rectal administration. 4) The specific antibody responses, immune complexes and complement values did not change in the sera of volunteers given AG which consisted of alternating cycles of twelve days of treatment with one suppository daily, and twelve days without treatment, in a clinical dose of 25 mg. Nevertheless, AG must be carefully prescribed as higher doses given to experimental animals induced adverse immunological effects.
在大鼠和豚鼠中研究了直肠给予马抗软骨-抗甲状旁腺免疫血清的Artroglobina(:AG,β和γ球蛋白组分)后的吸收情况及特异性抗体形成,在“一期研究”中使用志愿者血清进行了免疫测试。1)当将放射性标记的AG(125I-AG)直肠给予大鼠时,125I的血浆水平在2小时后达到最高值(占总剂量的3.1%),且总剂量的0.3%保留了与抗Fab抗体的反应性。2)在首次给药后间隔一定时间,以20mg/kg的剂量再次给予AG(相当于临床剂量的40倍)后,凝胶扩散和PCA试验在血清中给出阳性反应。从结果可知,直肠给予的AG在大鼠中主要诱导IgG或IgE抗体形成。3)直肠给予AG并未在已直肠给予AG的豚鼠中诱导全身性过敏反应。然而,静脉内激发在直肠给予AG治疗的动物中导致阳性过敏反应。这表明通过直肠给药使动物对AG产生了致敏作用。4)在以25mg的临床剂量给予AG的志愿者血清中,特异性抗体反应、免疫复合物和补体值没有变化,AG的给予方式为每天一枚栓剂,治疗12天,然后停药12天,交替循环。尽管如此,必须谨慎开具AG的处方,因为给予实验动物更高剂量会诱导不良免疫效应。