Patton J S, McCabe J G, Hansen S E, Daugherty A L
Pharmacology Department, Genentech, Inc., South San Francisco, California 94080.
Biotechnol Ther. 1989;1(3):213-28.
Recombinant methionyl human growth hormone (hGH) was administered intratracheally to adult rats, and serum concentrations of immunoreactive hGH were measured for up to 24 h. The mean absolute bioavailability was approximately 36% after 18h and was similar for doses of 0.75, 1.5, and 3 mg/kg. Peak serum hGH concentrations occurred at approximately 6 h after dosing. Tritiated hGH (3H-hGH) was used to follow the clearance of hormone from the lungs. Disappearance was linear with time and by 24 h approximately 70% of the radioactivity was gone from the lungs (elimination half-life = approximately 10.5h). Monomeric and aggregated hGH appeared to account for the majority of the residual 30% of radioactivity. Immunohistochemical localization of hGH in the alveoli suggested that the hormone was concentrated in a thin layer at the air-epithelial boundary. Pulmonary macrophages, which also stained for hGH, probably degrade hGH and thus account for some loss of material in the lungs. These studies suggest that the lung may be an alternative route for systemic delivery of recombinant proteins which are currently delivered by injection.
将重组甲硫氨酰人生长激素（hGH）经气管内给予成年大鼠，并在长达24小时内测定免疫反应性hGH的血清浓度。18小时后平均绝对生物利用度约为36%，0.75、1.5和3mg/kg剂量的生物利用度相似。给药后约6小时出现血清hGH浓度峰值。用氚标记的hGH（3H-hGH）追踪激素从肺中的清除情况。清除呈线性，到24小时时，约70%的放射性已从肺中消失（消除半衰期约为10.5小时）。单体和聚集的hGH似乎占剩余30%放射性的大部分。hGH在肺泡中的免疫组织化学定位表明，该激素集中在气-上皮边界的薄层中。也对hGH染色的肺巨噬细胞可能降解hGH，从而导致肺中部分物质的损失。这些研究表明，肺可能是目前通过注射给药的重组蛋白全身给药的替代途径。
