High molecular weight drugs in general, and peptides/proteins in parti
cular, are usually delivered by parenteral routes because they are poo
rly absorbed or degraded in the gastrointestinal tract. Long-term, rep
eated injections are often required because of the drug's short half-l
ife, and the chronic nature of many diseases. To optimize therapy, it
is essential to search for a non-parenteral route of drug administrati
on. We describe here the absorption and the systemic biological effect
of model drugs, after instillation into the uterus of the rat, In add
ition, we describe here results of calcitonin and insulin absorption f
rom controlled-release devices inserted in the rat uterus. The amount
and duration of the hypoglycemic and the hypocalcemic effects induced
by intrauterine delivery of insulin and calcitonin, respectively, were
equivalent to those obtained after subcutaneous injections. The thera
py of a number of clinically important diseases could benefit from thi
s discovery.