Comparison of the acute pharmacodynamic responses after single doses of ephedrine or sibutramine in healthy, overweight volunteers.

OBJECTIVE: With an increase in the incidence of obesity, tremendous effort has been devoted to the development of weight loss agents and the prospective surrogate markers of both a product's efficacy and safety. The objective of the present study was to compare the pharmacodynamic responses of ephedrine and sibutramine using surrogate markers of weight loss potential and potential adverse events. DESIGN AND SUBJECTS: The study was designed as a 5-way, randomized, double-blinded, placebo-controlled trial with 3 single doses of ephedrine sulfate (0.25, 0.5 and 1 mg x kg(-1)) followed by an open-labeled sibutramine (10 mg) treatment. Healthy, mildly overweight (BMI = 25) subjects were administered the respective treatment and pharmacokinetic and pharmacodynamic measurements (body surface temperature, resting metabolic rate, blood pressure, heart rate, glucose, glycerol, nonesterified fatty acids, triglycerides) were obtained for 8 hours post dose and for an additional 4 measurements during the sibutramine treatment period. RESULTS: Sibutramine treatment significantly increased resting metabolic rate compared to the placebo condition. Ephedrine significantly increased heart rate, systolic blood pressure and glucose but did not significantly affect other measurements. CONCLUSION: Both sibutramine and ephedrine have been shown to have weight loss potential, however, they elicit different metabolic and biochemical responses after a single dose. The nontherapeutic responses from these types of compounds may serve as a screening tool for the development of agents in the treatment of obesity.

Fast and reliable QRS alignment technique for high-frequency analysis of signal-averaged ECG.

The process of QRS alignment as required in signal-averaged ECG can impose serious limitations on the spectral range of the signal output. This effect depends basically on the particular alignment technique being used and on the level and type of noise present in the recorded ECG. In clinical studies where a wide-band (1000 Hz) ECG averager is required, the conventional QRS alignment technique, based on maximum coherence matching (MCM) with a template beat, may not perform consistently well. An alternative QRS alignment technique based on the accurate detection of a single fiducial point (SFP) in the bandpass filtered (3-30 Hz) QRS complex was developed. Using computer simulation methods, a comparative assessment of the frequency bandwidths (3 dB points) offered by both MCM and SFP techniques as a function of noise level (15-100 muRMS) and type (EMG and 50 Hz interference), was carried out. The results of the comparative assessment indicated a better performance by the SFP technique in all cases of noise. Hence, the SFP technique would perform more reliably for high-frequency analysis of a noisy ECG, especially when 50 Hz interference is high. Furthermore, SFP is considerably faster than MCM (about four times) when implemented digitally, and its analogue realisation is feasible. The SFP technique is suitable for late-potential analysis in the signal-averaged ECG.