Pharmacokinetics

Herb Drug interaction is a challenging concept, since the consumption of herbal and other drugs is not documented in patient’s profile. With this aspect the present study was designed to investigate the pharmacokinetic and Pharmacodynamic effect of neem leaf extract (NE) on the pharmacokinetics and pharmacodynamics of Glimepiride in diabetic rats. All the pharmacokinetic parameters such as Cmax, AUC0-n, AUCtot, t1/2 are increased and clearance and Vd are decreased when compared with control group. In Pharmacodynamic study the blood glucose levels are estimated, total antioxidant status in diabetic rats by using DPPH method and oral glucose toleranc test were performed. Combination has improved the total antioxidant status. The results revealed that combination of Glimepiride with neem leaf extract leads to enhancement of bioavailability of Glinepiride, this suggest that neem leaf extract might be beneficial as an adjuvant to Glimepiride in diabetic patients.

For the assessment effect of food on the pharmacokinetic parameters of Hydrochlorothiazide(HCTZ) data of reference product (12.5 mg capsule) from two bio-equivalence studies were combined and evaluated. 36 male healthy subjects participated in the fasting and non fasting study. Subjects received the drug product after 12 hours(h) overnight fast for the fasting study and after 30.0 minutes of high fat  breakfast for the non-fasting study. Blood samples were collected from time of dosing to 60 h of the post dosing at predefined time. Blood samples were analyzed for the concentration of the HCTZ by using validated LC/MS/MS technique. Food decrease the Cmax by about 28% and AUC by about 9%. While Tmax was delayed about 97%(from 2.185h to 4.320h). food prolonged the mean resident time of HCTZ. 

Microcapsules containing Fluvastatin Sodium having better drug retaining property. Most suitable for controlled release. Most satisfactory Fluvastatin Sodium microcapsules were subjected to pharmacokinetic evaluation with an objective to evaluate their drug release retarding and rate controlling efficiency in vivo. The rats were used for the in vivo bioavailability study. Ion exchange resins coated microcapsules of Fluvastatin Sodium was prepared by w/o/w emulsification technique. Fluvastatin Sodium release from Indion454 resins coated with eudragit RS100 microcapsules was slow and spread over 24 h. In the in vivo study, the absorption of fluvastatin sodium was slow over longer period of time with a rate constant (Ka) of 1.605 h-1. The mean residence time was observed from 6.5 h. Cmax was found to be 2.24µg/ml, tmax was found to be 6h, AUC was found to be 2.24µg/ml. From pharmacokinetic evaluation, Fluvastatin Sodium from resins coated microcapsules was released and absorbed slowly over longer period of time.