Hori R, Saito Y, Yasuhara M, Okumura K
J Pharmacobiodyn. 1984 Dec;7(12):910-6. doi: 10.1248/bpb1978.7.910.
Following injection of 125I-porcine insulin, 125I-aprotinin, 125I-salmon calcitonin, or 125I-(Asu1,7)-eel calcitonin into rats, high molecular weight (HMW) forms of these peptides were detected in serum or plasma when analyzed by gel chromatography. The conversion into HMW forms occurred after 1) intravenous bolus injection of insulin, aprotinin, or calcitonins, 2) intravenous infusion of insulin or aprotinin, and 3) subcutaneous injection of insulin, indicating that HMW forms were produced in the general circulation not in the subcutaneous tissue. Rechromatography of HMW forms produced in vivo from insulin or aprotinin showed the release of lower molecular weight component which was eluted at the same position of parent peptide, the immunoreactivity of the released component derived from insulin was almost the same as for insulin. These results suggest that the conversion of peptide drugs into HMW forms is generally occurred in vivo and they play a role as a depot in circulation.
向大鼠注射125I-猪胰岛素、125I-抑肽酶、125I-鲑鱼降钙素或125I-(Asu1,7)-鳗鱼降钙素后，通过凝胶色谱分析发现，血清或血浆中存在这些肽的高分子量（HMW）形式。这些肽转化为HMW形式发生在以下情况之后：1）静脉推注胰岛素、抑肽酶或降钙素；2）静脉输注胰岛素或抑肽酶；3）皮下注射胰岛素，这表明HMW形式是在体循环中产生的，而非皮下组织。对体内由胰岛素或抑肽酶产生的HMW形式进行再色谱分析，结果显示释放出低分子量成分，该成分在与母肽相同的位置被洗脱，源自胰岛素的释放成分的免疫反应性与胰岛素几乎相同。这些结果表明，肽类药物在体内通常会转化为HMW形式，并且它们在循环中起到储存库的作用。
