Effect of a deacyl gymnemic acid on glucose homeostasis & metabolic parameters in a rat model of metabolic syndrome.

Background & objectives: Metabolic syndrome (MS) comprises several cardio-metabolic risk factors, which include obesity, hypertension, hyperglycaemia, hypertriglyceridaemia and decreased HDL cholesterol. Leaf extract of Gymnema sylvestre has been shown to possess glucose lowering activity in animal models. This study was carried out to evaluate the efficacy of deacyl gymnemic acid (DAGA), active constituent of G. sylvestre, in a rat model of MS. Methods: Six groups consisting of six wistar rats in each, were studied. Group I received the normal diet, while the remaining five groups received high fructose diet (HFD ) for 20 days to induce MS. HFD was continued in these five groups for the next 20 days along with group II received vehicle solution, group III received pioglitazone and groups IV- VI received DAGA in variable doses. Systolic blood pressure (SBP) was measured using tail-cuff method. Oral glucose tolerance test (OGTT) was done at baseline and at days 20 and 40. Blood samples were collected for glucose, insulin and lipid profile. Results: Administration of HFD for 20 days resulted in weight gain (>10%), increase in SBP, fasting plasma glucose (FPG) and triglycerides fulfilling the criteria for MS. Administration of DAGA (200 mg/kg) reduced SBP and significantly improved the FPG and HOMA-IR (homeostatis model assessment-insulin resistance) with modest improvement in lipid profile without decrease in body weight similar to pioglitazone. Interpretation & conclusions: Our findings show that DAGA decreases SBP and improves parameters of glucose-insulin homeostasis in a rat model of MS induced by HFD. Further studies are required to elucidate the mechanism of action.

Changing chronobiology of cardiovascular outcome following prophylaxis.

Cardiovascular events like angina, myocardial infarction and stroke have shown an increasing occurrence in the morning hours. We did this pilot nested case control study to see for any change in the time pattern of occurrence of cardiovascular events among patients on prophylaxis. A pilot study was done and the demographic characters, history of cardiovascular diseases, time of occurrence of cardiovascular event, history of drug intake and compliance were noted. Eighty four patients on prophylaxis and 135 patients presenting for the first time reported during the study period. Age did not show any significant difference. More males were getting prophylaxis for stroke and for the combined cardiovascular events. Time distribution of events showed peak occurrence between 8 to 12 hr followed by 20 to 24 hr among those who were not on prophylaxis and reverse in those on secondary prophylaxis. Odds of developing cardiovascular events though was not significantly different, was higher between 16-20 hr (1.26), 20-24 hr (1.48) and 0-4 hr (1.22) among those on prophylaxis. Seventy eight patients were taking antihypertensives. This observation demands further studies to determine the cause of evening increase in cardiovascular event especially since very little is known regarding evening exaggeration of risk factors which is becoming relevant especially in those getting prophylaxis.

Antiepileptic TDM pattern at a tertiary care hospital in India.

Therapeutic drug monitoring, a comparatively new investigational procedure in clinical pharmacology, is considered very beneficial to epilepsy patients though it increase the health care cost. Aim of this study was to determine the pattern of use of antiepileptic drug level monitoring over the last 7 years in our tertiary care centre and to critically comment on its utility. Retrospective data audit of archived data from 1998 to 2004 and age, sex, estimated levels of phenytoin, carbamazepine and phenobarbitone by HPLC were noted down, tabulated and compared. Chi square test was used for analysis. Three thousand five jundred thirty four blood samples of patients requesting for 4213 estimations of phenytoin, phenobarbitone or carbamazepine were received. Among the obtained samples, 44.0% (1058) were of children, 68.0% (2402) were of males, 0.6% (22) patients were getting 3 and 18.0% (635) getting 2, antiepileptic medications. 13.0% (546) samples showed level in the toxic range and 39.0% (1653) in lower range. There was increasing demand observed for estimation of antiepileptic drugs, over the 7 years. The number of abnormal values of phenytoin, phenobarbitone and carbamazepine did not show any significant difference over the years. The pattern was similar to that observed in other countries.

The drug lag: new drug introductions in India in comparison to United States.

CONTEXT: Important drugs become available late in India, some much later, than in the United States. The prevailing trends in new drug introduction in India as compared to USA have been looked into this study. OBJECTIVES: To determine the trends in new drug introduction, both qualitative and quantitative, during the period, 1988 to 1999, in India. DESIGN: Data search, compilation and analysis. SOURCE: Various issues (1982-1997) of "Journal of the American Pharmaceutical Association" and "Indian Drug Manufacturers Association" Bulletin (1988-2000). MAIN OUTCOME MEASURES: Average drug lag, trends in drug lag over years (1988-1999), drug lag by therapeutic categories, drug lag by FDA classification of drugs. RESULTS: Average drug lag in India during the years 1988 to 1999 was 4.02 +/- 2.77 years. It has shown a decreasing trend over the years. Gastrointestinal drugs have the least drug lag (1.2 +/- 2 years). Cardiovascular drugs suffer the highest drug lag among therapeutic categories (5.21 +/- 2.2 years). 1AA drugs and 1P drugs (FDA classification) are priority drugs in India also. 1A drugs, which are important new therapeutics agents have been unfortunately neglected by drug developers and regulatory authorities in India. CONCLUSION: Important new drugs become available in India with a drug lag. This 'drug lag' has declined over the years. Qualitative analysis show that 1A class drugs, supposedly the most important category, has been the worst affected.