Peptide therapeutics: it’s all in the delivery

Abstract

Recent work has demonstrated that the route of administration affects the pharmacokinetics and biological activity of peptides. For example, the physiological profile of insulin consists of basal and prandial components with a small-scale oscillatory element. Insulin is used more efficiently when the pharmacokinetic profile mimics features of physiological release. Noninvasive administration of insulin by oral, transdermal, nasal and pulmonary routes resembles the relatively sharp peak and short duration of exposure of prandial release. The route of administration per se, can affect the response by avoiding first-pass metabolism or perhaps altering the timing in which the peptide reaches different sets of receptors. GLP-1 delivered by injection and inhalation produces different side effect profiles. Nonclinical studies on two potential treatments for obesity, oxyntomodulin and PYY 3-36, are also presented to illustrate the relationship between exposure and effect as functions of route of administration.