Digoxin: use pattern in Estonia and bioavailability of the local market leader.

BACKGROUND: In comparison with neighbouring Scandinavian countries, the use of digoxin in Estonia is high. The present study was carried out to determine the use pattern of digoxin in Estonia and bioavailability of the local market leader preparation in comparison with Lanoxin. METHOD: Drug use data were evaluated from the annual reports of wholesale companies. For the bioequivalence study, a single-blind cross-over randomised two-way single-dose comparative bioavailability study was performed using 14 healthy volunteers. Digoxin concentrations in serum samples and urine were measured by chemiluminescent competitive immunoassay. RESULTS: The use of digoxin in Estonia has increased by 35% during the period 1994-97. The steady market leader was the local generic drug. No statistically significant differences were found in any pharmacokinetic parameter between the generic preparation and Lanoxin. All parameters showed considerable variability. The total amount of drug excreted was the parameter with lowest inter- individual variation. CONCLUSION: The present study indicates that the generic digoxin preparation studied is bioequivalent to Lanoxin. The increasing use of digoxin in Estonia is not caused by low bioavailability of the local market leader but by therapeutic traditions.

Long-term administration of MC4 receptor antagonist HS014 causes hyperphagia and obesity in rats.

In this study we investigated the long term effects of a potent and selective melanocortin 4 (MC4) receptor antagonist (HS014) on food intake, body weight, body composition and blood glucose levels in adult rats. HS014 was injected i.c.v. either by twice-daily injections (2 x 1 nmol) for 6 days or administered by continuous infusion with osmotic minipumps (0.16 nmol/h) for 2 weeks. The results show a considerable increase in food intake and body weight after both of the treatments without any signs of tachyphylaxis. After 2 weeks of treatment with osmotic pumps, the HS014-treated rats (average weight 425g) had 20% higher body weight than the controls rats (average 360 g). When i.c.v. injections were terminated, the body weight of the twice-daily HS014-treated rats returned to the levels of control group, whereas the rats treated with continuous infusion of HS014 remained hyperphagic and still gained weight. Blood glucose levels in the rats treated with HS014 infusion were significantly increased. Analysis of body composition in HS014-infused rats indicated that body weight was increased due to fat deposits. These data show for the first time that chronic administration of exogenous MC4 receptor antagonist causes hyperphagia and severe obesity in rats. These data also indicate that the melanocortic control of food intake is very robust and suggest that changes induced by such treatment overcome negative feedback signals.