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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.

In vivo conversion of peptide drugs into high molecular weight forms.