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.

A simple and sensitive reverse phase high performance liquid chromatography (RP-HPLC) method was developed for the determination of glimepiride in rat serum. The assay involves one step liquid-liquid extraction with methanol. Gliclazide was used as an internal standard. Chromatographic separation was performed on a C 18 column using a mobile phase of methanol: 10 mM phosphate buffer (80:20 v/v) adjusted to pH 3.0 with orthophosphoric acid, at a flow rate of 1.0 ml/min and UV detection at 230 nm. The retention time of glimepiride and gliclazide was found to be 5.5 and 4.0 min and separation was complete in less than 10 min. The method was validated for linearity, accuracy and precision were found to be acceptable over the range of 0.5 -500 µg/ml for glimepiride. The method was found suitable to analyse rat serum samples for application in pharmacokinetic, pharmacodynamic, bioavailability/bioequivalence studies.

The effect of piperine on the pharmacokinetics and pharmacodynamics of glimepiride in normal as well as diabetic rats was studied. In normal and streptozotocin induced diabetic rats the combination of glimepiride with piperine increased all the pharmacokinetic parameters, such as C max , AUC 0-n , AUC total , t ½, and MRT, and decreased the clearance, Vd, markedly as compared with the control group. In pharmacodynamic studies, the combination of glimepiride with piperine provided significant protection against the diabetes induced alterations in the biochemical parameters. In addition, the combination of glimepiride with piperine also improved the total antioxidant status significantly in diabetic rats compared with piperine and glimepiride treated groups. The results revealed that a combination of glimepiride with piperine led to the enhancement of the bioavailability of glimepiride by inhibiting the CYP2C9 enzyme, which suggested that piperine might be beneficial as an adjuvant to glimepiride in a proper dose, in diabetic patients.

The effect of Boswellia serrata standardized extract (BSE) and Boswellic acids (BA) on the pharmacokinetics and pharmacodynamics of glimepiride in normal as well as diabetic rats was studied. In normal and streptozotocin induced diabetic rats the combination of glimepiride with BSE and BA increased all the pharmacokinetic parameters, such as Cmax, AUC0-n, AUCtotal, t½, MRT and decreased the clearance, Vd markedly as compared with the control group. In pharmacodynamic studies, the combination of glimepiride with BSE and BA provided significant protection against the diabetes induced alterations in the biochemical parameters. In addition, the combination of glimepiride with BSE and BA also improved the total antioxidant status and reduced the lipid peroxide levels significantly in diabetic rats compared with BSE, BA and glimepiride alone treated groups. The results revealed that a combination of glimepiride with BSE and BA led to the enhancement of the bioavailability of glimepiride by inhibiting the CYP2C9 enzyme, which suggested that boswellia might be beneficial as an adjuvant to glimepiride in a proper dose, in diabetic patients.

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