Bayley D, Temple C, Clay V, Steward A, Lowther N
Ciba Pharmaceuticals, Horsham, West Sussex, UK.
J Pharm Pharmacol. 1995 Sep;47(9):721-4. doi: 10.1111/j.2042-7158.1995.tb06730.x.
For therapeutic proteins such as interferon-alpha B/D, a non-parenteral route of delivery is desirable. Possible sites of administration include the various regions of the gastrointestinal tract and airways, and this paper reports the bioavailability of interferon-alpha B/D via these routes in the rat and rabbit. Apart from the stomach, detectable levels of interferon-alpha B/D in the serum were achieved via all routes. Bioavailabilities were less than 1%, except from the lung (6.8% in the rat) and nasal cavity (2.9% in the rabbit). Absorption from the gastrointestinal tract was similar for both species, but in the nasal cavity of the rabbit was sixfold that of the rat, and in the lung of the rat was tenfold that in the rabbit. Absorption from all routes, except the buccal cavity, resulted in detectable biochemical changes in the liver of the rabbit. Comparison with reports from other groups show differences in the extent of absorption of interferon-alpha B/D and of natural or homologous recombinant interferon-alpha. The non-parenteral delivery of biochemically active amounts of interferon-alpha B/D is thus demonstrated.
对于诸如干扰素-α B/D 之类的治疗性蛋白质,理想的给药途径是非肠道途径。可能的给药部位包括胃肠道和气道的各个区域,本文报道了干扰素-α B/D 通过这些途径在大鼠和兔子体内的生物利用度。除胃外,通过所有途径均可在血清中检测到可测水平的干扰素-α B/D。生物利用度均低于 1%,但肺(大鼠中为 6.8%)和鼻腔(兔子中为 2.9%)除外。两种物种从胃肠道的吸收情况相似,但兔子鼻腔的吸收是大鼠的六倍,大鼠肺的吸收是兔子的十倍。除口腔外,所有途径的吸收均导致兔子肝脏中出现可检测到的生化变化。与其他组的报告相比,干扰素-α B/D 以及天然或同源重组干扰素-α 的吸收程度存在差异。因此证明了以生化活性量进行干扰素-α B/D 的非肠道给药。