The influence of high-dose simvastatin and diltiazem on myocardium in rabbits: a haemodynamic study.
BACKGROUND
Simvastatin and diltiazem are often prescribed together for the treatment of hypercholesterolaemia in patients with hypertension and/or angina pectoris. However, diltiazem, a CYP3A inhibitor, is a well-recognized risk factor of skeletal muscle myopathy. It is not known whether such interaction also affects myocardial efficiency causing haemodynamic changes. The aim of the experiment was to establish the impact of simvastatin co-administered with diltiazem on the haemodynamic parameters after continuous infusion of dopamine.


METHODS
The experiments were performed on 28 New Zealand white rabbits. The animals were divided into four groups receiving: 0.2% MC - methylcellulose (control group); diltiazem; simvastatin; simvastatin + diltiazem, for 14 days (po). The following haemodynamic parameters were estimated: cardiac output index (CI), heart rate (HR), systolic blood pressure (SBP), mean blood pressure (MBP), diastolic blood pressure (DBP) and total peripheral resistance index (TPRI). The registration of haemodynamic parameters was performed by the Doppler method and during the experiments the animals were anaesthetized with α-chloralose (75 mg/kg bw) and urethane (500 mg/kg bw).


RESULTS
Dopamine did not cause a statistically significant increase in CI in rabbits receiving simvastatin alone. Diltiazem significantly increased CI if given simultaneously with simvastatin, which might suggest the improvement of cardiac efficiency resulting from such interaction.


CONCLUSIONS
The possibility of another mechanism of drug-drug interaction than the one based on CYP3A inhibition, and its impact on cardiac or skeletal muscle, might be considered.
Department of Biopharmacy, Medical University of Lodz, Poland.
Magdalena
M
Jasińska
Jacek
J
Owczarek
Daria
D
Orszulak-Michalak