Background: Hypertension and hypercholesterolemia are two main physiological
risk factors of cardiovascular disease, and commonly occur in combination. Multicompound
combination therapy is rational for the treatment of concurrent hypertension and
hypercholesterolemia, while telmisartan and pitavastatin calcium can be used as a potential
Objective: The aim of this paper is to study the intestinal absorption and absorption interaction
of telmisartan and pitavastatin calcium.
Methods: An HPLC method was developed and validated to determine telmisartan and
pitavastatin calcium in intestinal perfusate simultaneously. The in situ single-pass
perfusion in rats was utilized to investigate the effects of concentrations, intestinal segment
(duodenum, jejunum, ileum and colon) and co-administrated drugs on absorption.
Results: The effective permeability coefficient and the absorption rate constant of telmisartan
were higher in the duodenum as compared to other intestinal segments. However, the
intestinal absorption of pitavastatin calcium was not segmental dependent. The effective
permeability coefficient and absorption rate constant have no significant difference among
three concentrations of telmisartan, pitavastatin calcium individually and their combination.
Conclusion: The results showed that telmisartan and pitavastatin calcium were transported
passively, and telmisartan and pitavastatin calcium could be absorbed well in all intestinal
segments. The intestinal absorption parameters revealed the absence of any intestinal absorption
interaction when co-administered.
Lay Summary: Co-administration of telmisartan and pitavastatin calcium can provide a
potential therapeutic strategy for the treatment of concurrent hypertension and hypercholesterolemia.
We are investigating the intestinal interaction of these two drugs in rats using
the developed HPLC method and in situ single-pass perfusion technology. We will calculate
some parameters after administrating two types of drugs either separately or together,
which help reflect changes regarding intestinal absorption and penetration. Compared with
telmisartan and pitavastatin calcium administrated separately, if parameters significantly
change after co-administration, it proves the existence of the intestinal interactions. Moreover,
the results might contribute to clinic drug monitoring.