[Pharmacokinetics in healthy subjects of althiazide and spironolactone in a fixed combination for 2 doses]

Pharmacokinetic plasma curves of altizide (ALT), spironolactone (SPI) and two of the main metabolites of spironolactone, 7 alpha-thiomethyl-spirolactone (7TM) and canrenone (CAN) have been established in 12 healthy human volunteers (6 men and 6 women) after unique oral administration of 1 or 2 tablets of a combination of the two diuretic compounds: altizide (15 mg per tablet) and spironolactone (25 mg per tablets). Main pharmacokinetic parameters have been calculated using a biexponential (ALT and SPI) or a triexponential model (7TM and CAN). Spironolactone is rapidly absorbed. Plasma curves show Tmax respectively equal to 1.19 +/- 0.47 hours (1 tablet) or 1.21 +/- 0.46 (2 tablets). Spironolactone is rapidly metabolized as it is shown by the mean Tmax of metabolites: 7TM and CAN Tmax are respectively 1.56 +/- 0.45 hours and 2.54 +/- 1.06 hours after administration of 1 tablet, or 1.58 +/- 0.42 hours and 2.67 +/- 1.13 hours after administration of 2 tablets. The mean residence time (MRT) of ALT [4.94 +/- 1.14 hours (1 tablet) or 5.31 +/- 1.06 hours (2 tablets)] and SPI [1.81 +/- 0.45 hours (1 tablet) or 1.88 +/- 0.50 hours (2 tablets)] shows a rapid elimination of both drugs. SPI metabolites present higher MRT than the unchanged drug. 7TM MRT after administration of 1 or 2 tablets, are 24.51 +/- 15.35 hours and 18.11 +/- 11.87 hours, respectively. CAN MRT are 39.65 +/- 23.58 hours (1 tablet) and 38.93 +/- 24.58 (2 tablets). Statistical analysis shows no significant administration order effect on the different parametres. Student' t test shows a significant sex effect on CAN AUC, for both formulations.(ABSTRACT TRUNCATED AT 250 WORDS)