The pharmacokinetic (PK) and pharmacodynamic (PD) properties of
amylin can be assessed in various animal models; however, pigs are not
a suitable model for PD studies.
Unlike other known amylin receptor agonists such as salmon calcitonin
and pramlintide, NNC0174-0839 can bind to serum albumin and therefore
displays a significantly longer half-life. In mini-pigs, NNC0174-0839
displays a terminal half-life (T1/2) of 110 h following a s.c.
administration of a single dose of 10 nmol/kg.
The pharmacodynamic properties of amylin such as appetite reduction
and reduction of body weight can be studied in rats. The effect on
food intake (FI) in lean Sprague Dawley rats after s.c. administration
of a single dose of NNC0174-0839 given prior to onset of the dark
phase is shown in the table below. The reduction in accumulated food
intake is reported relative to vehicle-treated rats within the same study.
reduction 0-24 h
reduction 24-48 h
reduction 0-48 h
Amylin analogues can cause gastro-intestinal side effects such as
nausea and feeling of malaise. Therefore, dose escalation should be
introduced if doses higher than 10 nmol/kg is being investigated in
rats. Doses can be escalated every third day.
NNC0174-0839 also induce acute hypocalcaemia in young rodents,
especially in rats. This can potentially lead to serious side effects
and even death, so stress should be avoided prior to dosing and
Sprague Dawley rats from Janvier Labs should not be used for in
vivo experiments since these are very sensitive to the
hypocalcaemia-inducing properties of NNC0174-0839.