Pharmacokinetic and Pharmacodynamic Interaction of Boswellic Acids and Andrographolide with Glyburide in Diabetic Rats: Including Its PK/PD Modeling

Abstract

The effect of boswellic acids (BA) and andrographolide (AD) on the pharmacokinetics and pharmacodynamics of glyburide in normal as well as in streptozotocin-induced diabetic rats was studied. In normal and diabetic rats, the combination of glyburide with BA or AD increased significantly (p < 0.01) all the pharmacokinetic parameters, such as Cmax, AUC0-n, AUCtotal, t1/2, and mean residence time, and decreased the clearance, Vd, markedly as compared with the control group. In rat liver, microsomes BA and AD have shown CYP3A4 inhibitory activity significantly (p < 0.01), compared with the vehicle group. The increase in hypoglycemic action by concomitant administration of glyburide with BA or AD was more in diabetic rats than when the drugs were used singly and with the control group, which suggests the enhancement of glucose reduction capacity of glyburide in diabetic rats along with BA or AD. In PK/PD modeling of BA and AD with glyburide, the predicted PK and PD parameters are in line with the observed PK and PD parameters. The results revealed that BA and AD led to the PK/PD changes because of glyburide-increased bioavailability and because of the inhibition of CYP3A4 enzyme. In conclusion, add-on preparations containing BA or AD may increase the bioavailability of glyburide, and hence the dose should be monitored.

Effect of Boswellia on Adjuvant Induced Rheumatoid Arthritis in Experimental Animals

“…The manifestations peaked between days 18 and 20. There were no significant differences in arthritic score or edema between the two groups before BC or vehicle administration on day 16…”

“…After the observation period, all animals was euthanized and a gross necropsy was performed. All observations were performed by investigators who were blinded to treatment group assignments [16].…”

Pharmacokinetic and Pharmacodynamic Interaction of Andrographolide and Standardized Extract of Andrographis paniculata (Nees) with Nabumetone in Wistar Rats

“…The data indicates that AN and some ingredients of APE might have decreased the plasma concentration of 6‐MNA in rats. In a recent study, AN has shown to affect the metabolism of glyburide by the inhibition of CYP3A4 (Samala and Veeresham, ). The decrease in C max and AUC of 6‐MNA is more with AN + NAB treated group compared to APE + NAB treated group.…”

Pharmacologically relevant drug interactions of sulfonylurea antidiabetics with common herbs

“…Use Andrographis paniculata (Androdrographolide) with caution in patients taking sulfonylureas to avoid the risk of hypoglycemia (155).…”

“…The hypoglycemic effect of glyburide enhanced considerably by the coadministration with androdrographolide. The herbal preparations containing A. paniculata (androdrographolide) should be used in patients taking sulfonylureas with special attention to avoid the risk of hypoglycemia (155).…”