| Abstrakt: |
A single-dose, crossover, comparative study of 25- and 100-mg spironolactone tablets was undertaken in 39 healthy males. Following a total dose of 200 mg, blood samples were drawn at 0, 1, 2, 3, 4, 6, and 24hr and a single collection of urine was taken after the initial 6hr. The dethioacetylated active metabolite was measured in these specimens and was employed as the indicator of drug absorption and elimination. A comprehensive statistical analysis, including: (a)multivariate hour-by-hour comparisons with plasma aldadiene levels, (b)comparisons with total plasma area and total urinary metabolite level, (c)bivariate comparisons with peak plasma aldadiene levels, and (d)urinary sodium-potassium ratio responses, examines the question of the biological equivalence of these two spironolactone preparations. The primary discriminators for comparing the two dosage forms were found to be plasma metabolite levels at Hours 3 and 4, peak plasma metabolite level, and total 24-hr area under the plasma level curve. Moreover, a single plasma level by itself does not appear to be sufficient to test for biological equivalence, so correlations among levels should not be ignored. The mean peak plasma metabolite levels for the 25- and 100-mg formulations reached 67.8 and 61.6 μg/100 ml, respectively, each at the same mean time of 160min. |
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