Shailesh K. Mody

A Comprehensive Review on Pharmacotherapeutics of Herbal Bioenhancers

In India, Ayurveda has made a major contribution to the drug discovery process with new means of identifying active compounds. Recent advancement in bioavailability enhancement of drugs by compounds of herbal origin has produced a revolutionary shift in the way of therapeutics. Thus, bibliographic investigation was carried out by analyzing classical text books and peer-reviewed papers, consulting worldwide-accepted scientific databases from last 30 years. Herbal bioenhancers have been shown to enhance bioavailability and bioefficacy of different classes of drugs, such as antibiotics, antituberculosis, antiviral, antifungal, and anticancerous drugs at low doses. They have also improved oral absorption of nutraceuticals like vitamins, minerals, amino acids, and certain herbal compounds. Their mechanism of action is mainly through absorption process, drug metabolism, and action on drug target. This paper clearly indicates that scientific researchers and pharmaceutical industries have to give emphasis on experimental studies to find out novel active principles from such a vast array of unexploited plants having a role as a bioavailability and bioefficacy enhancer. Also, the mechanisms of action by which bioenhancer compounds exert bioenhancing effects remain to be explored.

Recent developments in receptor tyrosine kinases targeted anticancer therapy

Novel concepts and understanding of receptors lead to discoveries and optimization of many small molecules and antibodies as anti-cancerous drugs. Receptor tyrosine kinases (RTKs) are such a promising class of receptors under the investigation in past three decades. RTKs are one of the essential mediators of cell signaling mechanism for various cellular processes. Transformations such as overexpression, dysregulation, or mutations of RTKs may result into malignancy, and thus are an important target for anticancer therapy. Numerous subfamilies of RTKs, such as epidermal growth factor receptor, vascular endothelial growth factor receptor, fibroblast growth factor receptors, insulin-like growth factor receptor, and hepatocyte growth factor receptor, have been being investigated in recent years as target for anticancer therapy. The present review focuses several small molecules drugs as well as monoclonal antibodies targeting aforesaid subfamilies either approved or under investigation to treat the various cancers.

Determination of orbifloxacin in sheep plasma by high performance liquid chromatography with ultraviolet detection after intravenous and intramuscular administration

INTRODUCTION Single-dose pharmacokinetics of orbifloxacin (2.5mg/kg body weight) were determined in clinically normal female Patanwadi sheep (n=6) following intravenous and intramuscular administration. METHODS Orbifloxacin concentrations were determined by high performance liquid chromatography with ultraviolet detection. The concentration-time data were analyzed by non-compartmental kinetic method. RESULTS AND DISCUSSION Following a single intravenous injection, an elimination half-life (t(1/2β)) of 8.31±0.102h. Steady-state volume of distribution (Vd(ss)) and total body clearance (Cl(B)) were 3.09±0.282L/kg and 0.158±0.006L/kg/h, respectively. Following intramuscular administration, an elimination rate constant (β), the area under the curve from zero to infinity (AUC(0-∞)) and the mean absorption time (MAT) were 0.015±0.001h(-1), 23.49±1.722μg·h/mL and 7.50±0.58h, respectively. The peak plasma concentration (C(max)) of 1.81±0.005µg/mL was achieved at 1.00±0.00h. The mean residence time (MRT) was 26.25±1.083h and the absolute bioavailability was 150.8±12.35%, respectively. Orbifloxacin could be useful for the treatment of bacterial infections in sheep that are sensitive to this drug.

Transgenic Plant Vaccine: A Breakthrough in Immunopharmacotherapeutics

Transgenic plant vaccines are genetically engineered plant vaccines in which a selected gene is encoded for the desired antigen and modified which when taken orally elicits a strong immune response in the body. Plant-cellproduced vaccines are inherently safe because they pose no risk of microbiologic contamination associated with animal-derived vaccines and eliminate the risk of pathogenicity, reversion to virulence and shedding. Oral delivery stimulates mucosal immunity (the first line of defense) in the tissues lining the respiratory system and eliminates injection-related hazards. Plants structure may help in maintaining the antigenic property even after degradation in intestine. Plenty of availability of plants makes the vaccine production of low cost apart from low cost in storage and transportation. They act through different mechanism of action mainly stimulating the lymphoid structure in the intestine. This review highlights the development of transgenic plant vaccine, its action, and certain important diseases of animals, poultry and humans and status of plant vaccine developed against them.

Biochemical Alteration Induced After Intramuscular Administration of LongActing Moxifloxacin in Sheep

The present study was conducted with objective to study biochemical alterations induced after single intramuscular administration of long acting moxifloxacin at the dose rate of 7.5 mg/kg body weight in six healthy male sheep. After deep intramuscular injection of moxifloxacin, blood samples in collected K3EDTA at 0, 6, 12 hour and 2, 3,4, 5,6,7th day after treatment were analyzed for biochemical Aspartate Aminotransferase (AST) Alanine aminotransferase (ALT), Alkaline Phosphatase (AKP), Acid Phosphatase (ACP), plasma creatinine, plasma Creatine kinase-MB, Blood glucose and Total bilirubin) analysis. The results of the study clearly demonstrated that single intramuscular administration of long acting moxifloxacin in sheep at 7.5 mg/kg body weight did not cause any significant change in values of biochemical parameters in sheep with total absent of clinical signs of adverse reactions or toxicity.

Disposition Kinetic of Moxifloxacin following Intravenous, Intramuscular, and Subcutaneous Administration in Goats.

The present study was carried out to investigate disposition kinetics of moxifloxacin following single-dose intravenous (i.v.), intramuscular (i.m.), and subcutaneous (s.c.) administration at a dose rate of 5 mg/kg of body weight (b.wt.) in goats. Plasma samples collected after treatments were analyzed for drug concentration using high-performance liquid chromatography (HPLC). After i.v. administration, distribution of the drug was rapid and wide as reflected by high steady-state volume of distribution. Drug elimination was relatively faster with a total body clearance of 0.59 ± 0.03 L/h/kg. Following i.m. injection, the drug has shown the rapid and near-to-complete absorption with bioavailability of 98.20 ± 3.96 per cent. The maximum plasma drug concentration (Cmax) of 1.21 ± 0.04 μg/mL was attained at 1 h (Tmax). The drug was widely distributed as reflected by high apparent volume of distribution. The elimination half-life (t 1/2β) of the drug was 6.26 ± 0.08  h. Following s.c. administration, the drug was rapidly absorbed (Cmax: 1.16 ± 0.02 μg/mL; tmax: 1 h) and slowly eliminated from the body. The elimination half-life and total body clearance (ClB) were 5.61 ± 0.10 h and 0.60 ± 0.03 L/h/kg, respectively. The bioavailability of moxifloxacin following s.c. administration was 90.44 ± 3.96 per cent.

Plasma Disposition of Conventional and Long-Acting Moxifloxacin in Sheep after Intravenous Administration

This study describes disposition of long-acting moxifloxacin and conventional formulations of moxifloxacin in sheep after intravenous administration in five male sheep. Long acting moxifloxacin solution (10% moxifloxacin in solution with L-arginine, N-butyl alcohol, and benzyl alcohol) and conventional moxifloxacin (10%) were injected in jugular vein. Blood samples were collected from contralateral jugular vein in test tubes containing 30–50 IU heparin (anticoagulant) periodically from 0.083 to 72 h of drug administration. Drug concentrations in plasma were determined using High-Performance Liquid Chromatography (HPLC) with fluorescence detector. The mobile phase consisted of a mixture of buffer (10 gm of tetrabutyl ammonium hydrogen sulphate per liter-deionised water) and acetonitrile (80 : 20). The buffer was 0.067M of disodium hydrogen phosphate with pH of 7.5. The flow rate was 1 mL·min−1 at ambient temperature. The effluent was monitored at 296 nm excitation and 504 nm emissions wavelength. HPLC with fluorescence detector method for plasma moxifloxacin assay was standardized with specific modification for plasma of sheep in the present study. After single-dose intravenous administration of long acting moxifloxacin the plasma concentration of 0.016 ± 0.001 μg·mL−1 was maintained for up to 72 h. Conventional formulation of moxifloxacin remained in body for up to 24 h of drug administration with the level of 0.015 ± 0.005 μg·mL−1.