Rectal administration of insulin.

Abstract

According to recent statistics for the time span 1951-1970, the mortality ratio of diabetics to non-diabetics was 335% (46). For those diabetics who were younger than 15 years when entering the study, the mortality ratio was 1127%, with a mean life expectancy of another 32 years, as compared to 59 years for non-diabetics. Among the major causes of disablement and early death are ischemic heart disease, retinopathy, nephropathy, peripheral vascular disease and neuropathy. In spite of newer, more potent and highly purified insulins, development of human insulin, change of once-daily injection to twice-daily insulin therapy (47), and the introduction of portable insulin infusion pumps, diabetes is still a high-risk disease, far from being controlled. Considering that the present mode of insulin administration is by the subcutaneous route by which the insulin is presented to the body in a nonphysiological manner, because the insulin is peripherally administered to the systemic circulation instead of portally, new therapeutic ways for insulin administration are worth study. During the past years, considerable interest has arisen in the rectal route of administration. Based on a physiological-kinetic model presented in this paper, utilization of the first-pass effect inherent to the rectal anatomy offers a physiological insulin input via the rectal route of administration. A review on the present state of rectal insulin administration is given, and experimental data from our laboratories are presented. The usefulness of sorption promoters on rectal insulin absorption is discussed. The "effectiveness" of rectal insulin preparations is suggested to be evaluated by four criteria: the pharmacological availability via the area under the % glucose reduction-time profile, the maximum glucose concentration reduction, Cmax, the time to reach the maximum reduction, tmax, and the mean residence time for glucose reduction, MRT.