Evaluating average bioequivalence using methods for high variability drugs: a case study.

The purpose of this study was to determine if different methods for average bioequivalence in high variability drugs coincide or not in their conclusions when applied to the same dataset, and to discuss the method validity and reliability of the conclusions. Different approaches for the evaluation of average bioequivalence were applied to the results of a bioavailability trial on the diuretic drug Furosemide. These methods included widening the bioequivalence limits according to regulatory recommendations, scaling the limits and scaling the bioequivalence statistic, jointly with evaluating alternative bioavailability measures. The methods to establish the bioequivalence limits were also combined with some alternative methods to construct confidence intervals. The decision on bioequivalence depends much more on the bioavailability measures than on the statistical approach. The reliability of the final decision lies mainly in the interpretation of these measures and on the special characteristics of each drug.

[Myxoma of the left ventricle: Its diagnosis by 2-dimensional echocardiography]. / Mixoma de ventrículo izquierdo: diagnóstico mediante ecocardiografía bidimensional.

We report a patient who presented with focal neurologic findings. Bidimensional echocardiography disclosed a mass with aspect of myxoma located in the left ventricle. Surgical excision allowed confirmation of the diagnosis.

[Doctor's-office blood pressure, home blood pressure, ergometry blood pressure and 24-hour blood pressure. The correlations with the echocardiographic parameters of heart muscle mass]. / Sprechstundenblutdruck, Heimblutdruck, Ergometer-Blutdruck und 24-Stunden-Blutdruck. Korrelationen mit echokardiographischen Parametern der Herzmuskelmasse.

In 62 untreated hypertensives (31 men, 31 women; median age 40 [17-57] years) blood pressures (BP) were measured in the doctor's office, at home (self-measured) and every 15 min during 24-hour monitoring (by portable automated oscillometry), the results being compared with echocardiographic measurements of ventricular septal thickness (VST), left ventricular muscle mass (LVM) and left ventricular mass index (LVMI), in 41 of them also during and 5 min after 100 W bicycle ergometry. In the total cohort, 24-hour values correlated better with diastolic VST (systolic: r = 0.706, P less than 0.00001; diastolic: r = 0.507, P less than 0.0001) than office BP (systolic: r = 0.381, P less than 0.01; diastolic: r = 0.177, not significant) and home BP (systolic: r = 0.477, P less than 0.0001; diastolic: r = 0.371, P less than 0.05). In the 41 exercised hypertensives the correlation with echocardiographic values was less close than with their 24-hour BP, but slightly better than with office and home BP. Systolic BP correlated better than diastolic BP with echocardiographic values. VST generally correlated better with BP than LVM and LVMI. It is concluded that (1) 24-hour BP values correlate more closely with LVM than any other noninvasive BP measurement; (2) VST is affected more by systolic than diastolic BP; and (3) VST more specifically reflects the influence of BP on myocardial structure than does LVM and LVMI.

The influence of nicardipine on left ventricular hemodynamics and compliance in patients with coronary heart disease.

The hemodynamic effects of nicardipine were studied in 10 normotensive patients (nine men, one woman; age 43-70 years, mean 56 years) and five patients with mild to moderate hypertension (four men, one woman; age 46-72 years, mean 62.8 years); in all patients coronary heart disease was confirmed by angiography. Hemodynamic parameters were determined before and after intravenous administration of nicardipine in cumulative doses of 2.5, 7.5, and 12.5 mg for 10 min each. Nicardipine significantly reduced systolic aortic pressure, diastolic aortic pressure, and mean aortic pressure in normotensive patients [139 +/- 8.7 vs. 114 +/- 9.2 mm Hg (p < 0.001), 73 +/- 9.1 vs. 56 +/- 7.9 mm Hg (p < 0.001), 97 +/- 7.8 vs. 7.8 +/- 7.9 mm Hg (p < 0.001), respectively] and in hypertensive patients [166 +/- 7.4 vs. 128 +/- 8.6 mm Hg (p < 0.001), 83 +/- 9.4 vs. 56 +/- 10.9 mm Hg (p < 0.001), 110 +/- 15.5 vs. 78 +/- 12.0 mm Hg (p < 0.001), respectively]. Systemic vascular resistance was decreased significantly in hypertensive patients [1,363 +/- 188 vs. 707 +/- 137.7 dyn sec cm-5 (p < 0.001)] and in normotensive patients [1,110 +/- 225.3 vs. 682 +/- 92.4 dyn sec cm-5 (p < 0.001)]. Heart rate increased from 68 +/- 6.8 to 83 +/- 11.4 beats/min (p < 0.001) in normotensive patients but the increase from 72 +/- 14.7 to 80 +/- 14.2 beats/min in hypertensive patients was not significant. Mean pulmonary artery pressure did not change significantly in hypertensive patients and increased slightly in normotensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)