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.

A meta-analysis of controlled clinical trials comparing low-molecular weight heparins with unfractionated heparin in unstable angina.

BACKGROUND: Unfractionated heparin has been used extensively for the treatment of unstable angina/non-Q wave myocardial infarction but it has several disadvantages. Low-molecular weight heparins are now recommended although they are 3-5 times costlier than unfractionated heparin since they are convinient to administer and do not require activated thromboplastin time monitoring. Whereas enoxaparin, a low-molecular weight heparin, has been demonstrated to be superior to unfractionated heparin, the results of other low-molecular weight heparins have not been so convincing. METHOD AND RESULTS: Through manual, MEDLINE and EMBASE search, we identified five randomized trials (excluding enoxaparin trials) that compared low-molecular weight heparins with unfractionated heparin in unstable angina. The prespecified efficacy end point of interest included a composite of death, myocardial infarction, recurrent angina and urgent revascularization. The safety end point was taken as a composite of major hemorrhage, minor hemorrhage, thrombocytopenia, allergic reaction and any other adverse event. We calculated odds ratio (95% confidence interval) for each trial for the composite end point, and the pooled odds ratio (95%) confidence interval) was calculated using two established methods of meta-analysis, the Mantel-Haenszel-Peto method and the DerSirmonian-Laird method. Both the methods yielded similar odds ratio (95% confidence interval). Separate odds ratio were calculated for efficacy and safety end points. There was a nonsignificant reduction in the incidence of the composite efficacy end point: the odds ratio (95% confidence interval) was 0.83 (0.70-0.99: p=0.08). The odds ratio (95% confidence interval) for the safety data was 0.78 (0.69-1.26: p=0.33). CONCLUSIONS: No statistically significant difference was observed when the efficacy and safety of low-molecular weight heparins were compared with those of unfractionated heparin. A cost-effectiveness analysis of low-molecular weight heparins versus unfractionated heparin must be done urgently to establish more firmly the place of low-molecular weight heparins in the management of unstable angina.

Effect of acute and chronic administration of L-arginine on morphine induced inhibition of gastrointestinal motility.

Effect of acute and chronic administration of L-arginine on morphine induced gastrointestinal inhibition was tested in rats. In the test for acute effect, L-arginine (200 mg/kg, i.v.) was given 10 minutes before the charcoal meal test. In the test for chronic effects, L-arginine (200 mg/kg, i.v.) was given twice a day for 4 days. Charcoal meal test was done on the fifth day. Morphine was administered 45 minutes before the charcoal meal test. Results showed that acute administration of L-arginine did not affect the morphine's action on the GIT. In contrast, chronic administration of L-arginine reversed the morphine induced decrease in gastrointestinal motility. The reversal was however, not complete. This data suggests that inhibition of NO may be one of the mechanism of morphine induced constipation.

Effect of the 5-HT3 receptor antagonist ondansetron on amphetamine-induced hyperactivity and stereotypy in rats.

The effects of different doses of ondansetron (0.1, 0.5, 1, 2 mg/kg) administered intra-peritoneally were studied on amphetamine-induced hyperactivity and stereotypy in wistar rats. Ondansetron was administered 30 minutes prior to d-amphetamine (3 mg/kg, i.p.). Ondansetron in doses of 0.5 and 1 mg/kg significantly decreased the mean number of head dippings and crossings in the hole board test and in doses of 0.1 and 0.5 mg/kg significantly decreased the average stereotypic score. Since the hyperactivity and stereotypy are dopamine mediated, the effect of ondansetron to reduce these states suggests a potential role for ondansetron in conditions with dopamine excess.