Influence of Single and Multi Dose Treatment of Glipizide on Pharmacokinetics and Pharmacodynamics of Irbesartan in Normal and Hypertensive Rats.

PURPOSE: The present study was carried out to investigate the pharmacokinetic and pharmacodynamic drug interaction of irbesartan with glipizide after single and multi dose treatment in normal and hypertensive rat models to evaluate the safety and effectiveness of the combination. METHODS: The study was conducted on normal and 10% fructose solution induced hypertensive rats. Irbesartan and glipizide were administered orally for 7 days and on 8th day blood samples were collected for 12 h at regular time intervals from irbesartan alone and in combination with glipizide treated groups. The blood samples were analyzed for various pharmacokinetic and pharmacodynamic parameters. RESULTS: Irbesartan caused marked reduction in blood pressure in hypertensive rats. The combination of irbesartan and glipizide in hypertensive rats produce significant change in blood pressure (pharmacodynamic) and also significance in pharmacokinetic parameters of irbesartan with glipizide in single dose and multiple doses. CONCLUSION: The results of present study demonstrated that the synergistic activity of irbesartan with glipizide was observed.

Effect of ethanolic extracts of Justicia neesii Ramam. against experimental models of pain and pyrexia.

OBJECTIVE: The main objective of this study is to evaluate the analgesic and anti-pyretic activities of ethanolic extracts of Justicia neesii Ramam. by different experimental models. MATERIALS AND METHODS: The analgesic activity of plant extract was evaluated against thermal and chemical stimulus induced by Eddy's hot plate and acetic acid respectively in mice. Brewer's yeast induced pyrexia was used to evaluate the antipyretic activity in rats and TAB vaccine induced pyrexia was used to evaluate the antipyretic activity in rabbits. RESULTS: In the hot plate model 400 mg/kg p.o. dose of J. neesii has shown its maximal effect at 3 h. The results are significant (P < 0.05) and comparable to the values of standard drug pentazocine (30 mg/kg i.p.). In acetic acid induced writhing model 400 mg/kg p.o. of plant extracts have shown highly significant activity (P < 0.001) and better than standard drug indomethacin (10 mg/kg p.o.). The 400 mg/kg p.o. dose of plant extract has given significant results against both yeast induced pyrexia and TAB vaccine induced pyrexia (P< 0.01 and 0.05 respectively). These values are comparable to that of paracetamol 100 mg/kg p.o. standard dose. CONCLUSION: This study shows that the ethanol extract of J. neesii has significant analgesic and antipyretic activity.

Development and evaluation of a novel biodegradable sustained release microsphere formulation of paclitaxel intended to treat breast cancer.

OBJECTIVE: The objective of this study was to develop a novel 1 month depot paclitaxel (PTX) microspheres that give a sustained and complete drug release. MATERIALS AND METHODS: PTX loaded microspheres were prepared by o/w emulsion solvent evaporation technique using the blends of poly(lactic-co-glycolic acid) (PLGA) 75/25, polycaprolactone 14,000 and polycaprolactone 80,000. Fourier transform infrared spectroscopy was used to investigate drug excipient compatibility. Compatible blends were used to prepare F1-F6 microspheres, the process was characterised and the optimum formulation was selected based on the release. Optimised formulation was characterised for solid state of the drug using the differential scanning calorimetry (DSC) studies, surface morphology using the scanning electron microscopy (SEM), in vivo drug release, in vitro in vivo correlation (IVIVC) and anticancer activity. Anticancer activity of release medium was determined using the cell viability assay in Michigan Cancer Foundation (MCF-7) cell line. RESULTS: Blend of PLGA with polycaprolactone (Mwt 14,000) at a ratio of 1:1 (F5) resulted in complete release of the drug in a time frame of 30 days. F5 was considered as the optimised formulation. Incomplete release of the drug resulted from other formulations. The surface of the optimised formulation was smooth and the drug changed its solid state upon fabrication. The formulation also resulted in 1-month drug release in vivo. The released drug from F5 demonstrated anticancer activity for 1-month. Cell viability was reduced drastically with the release medium from F5 formulation. A 100% IVIVC was obtained with F5 formulation suggesting the authenticity of in vitro release, in vivo release and the use of the formulation in breast cancer. CONCLUSIONS: From our study, it was concluded that with careful selection of different polymers and their combinations, PTX 1 month depot formulation with 100% drug release and that can be used in breast cancer was developed.

Neuroprotective effects of meloxicam and selegiline in scopolamine-induced cognitive impairment and oxidative stress.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by a gradual decline in memory associated with shrinkage of brain tissue, with localized loss of neurons mainly in the hippocampus and basal forebrain, with diminished level of central cholinergic neurotransmitter-acetylcholine and also reported to be associated with accumulation of ubiquitinated proteins in neuronal inclusions and also with signs of inflammation. In these disorders, the abnormal protein aggregates may themselves trigger the expression of inflammatory mediators, such as cyclooxygenase 2 (COX-2). In the present study, the effects of Meloxicam, Selegiline, and coadministration of these drugs on scopolamine-induced learning and memory impairments in mice were investigated. Rectangular maze test, Morris water maze test, Locomotor activity, and Pole climbing test were conducted to evaluate the learning and memory parameters. Various biochemical parameters such as acetylcholinesterase(AChE), TBARS assay, catalase activity, and DPPH assay were also assessed. The present study demonstrates that Meloxicam, Selegiline, and co-administration of these test drugs had potential therapeutic effects on improving the antiamnesic activity in mice through inhibiting lipid peroxidation, augmenting endogenous antioxidant enzymes, and decreasing acetylcholinesterase activity in brain. The memory enhancing capacity of the drugs was very significant when compared to disease control (P < 0.001).