Date of Defense

Winter 2-1992

Department

Biological Sciences

First Advisor

Leonard Ginsberg, Biological Sciences

Second Advisor

Mary Ruwart, Upjohn Company

Third Advisor

Karim Essani, Biological Sciences

Abstract

Small peptides, such as renin inhibitors, are rapidly cleared from the systemic circulation after administration, making maintenance of the blood levels of the peptide for long periods of time difficult. To test whether the subcutaneous route of administration offers sustained release for peptides, solutions and suspensions of the renin inhibitory peptides were given subcutaneously to unanesthetized rats with pre-implanted venous cannula. Blood profiles were monitored over the next eight hours with a previously reported activity assay (Ruwart et al, 1990). The rate of absorption from the subcutaneous pocket was found to be dependent upon the amount of drug in solution rather than the structural modifications of the peptides. Thus, peptides in solution were rapidly absorbed. Peptides in suspension were absorbed only as they redissolved and attained steady-state sera levels which were maintained over time periods, the length of which was determined by dose. Modeling studies indicated that sera profiles of the peptides could be predicted, to a first approximation, from known solubilities and pharmacokinetic clearances.

Access Setting

Honors Thesis-Campus Only

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