Pharmacokinetic and pharmacodynamic interaction of rosuvastatin calcium with guggulipid extract in rats

Abstract EN

Background & objectives : rosuvastatin calcium (RC) is a potent and competitive synthetic inhibitor of HMG-CoA reductase used for the treatment of dyslipidemia.

guggulipid obtained from Commiphora mukul is used in the treatment of a wide variety of diseases such as atherosclerosis, hypercholesterolemia, rheumatism, and obesity.

the present study evaluates the pharmacokinetic and pharmacodynamic interactions between RC and the standardized guggulipid extract in rats.

materials and methods : the guggulipid extract was standardized for the presence of guggulsterones.

the pharmacokinetic interaction was determined after a single dose administration of RC alone or in combination with the guggulipid extract or after multiple-dose administration of RC alone or RC along with the guggulipid extract for 14 days.

to determine the pharmacodynamic interaction, RC and guggulipid extract were administered to hyperlipidemic rats for 14 days.

the level of significance was determined using unpaired student’s t-test, one way ANOVA, the post-ANOVA Tukey test.

Results: Standardization of guggulipid extract showed it contains 7.5%w/w of guggulsterones.

Guggulipid extract increased the bioavailability of RC in both single-dose and multiple-dose studies.

Guggulipid extract reduced the rate of absorption (Ka) of RC but showed an increase in maximum serum concentration (Cmax).

An in-vitro study using isolated rat intestine revealed that guggulipid extract decreased the rate of absorption of RC in the intestinal lumen.

the hypolipidemic activity of RC was augmented by the guggulipid extract in hyperlipidemic rats.

interpretation & conclusion : therefore it is concluded that guggulipid extract increases the bioavailability of RC by delaying its Ka and augments its hypolipidemic action.

However, it is recommended that a combination of RC with guggulipid extract should be used only after an adverse effect(s) of this combination are determined.