title: [Pharmacokinetics in healthy subjects of althiazide and spironolactone in a fixed combination for 2 doses].
abstract: 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)
authors.affiliation: Laboratoire d'Etudes du Métabolisme des Médicaments, Département de Biologie CEN-Saclay, Gif-sur-Yvette.
authors.forename: J L
authors.initials: JL
authors.lastname: Doignon
authors.forename: J M
authors.initials: JM
authors.lastname: Grognet
authors.forename: J J
authors.initials: JJ
authors.lastname: Thébault
authors.forename: M
authors.initials: M
authors.lastname: Caplain
authors.forename: M H
authors.initials: MH
authors.lastname: Capron
authors.forename: B
authors.initials: B
authors.lastname: Pelletier
authors.forename: M
authors.initials: M
authors.lastname: Wehrlen
authors.forename: M
authors.initials: M
authors.lastname: Istin
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000493:pharmacokinetics*; D001581:Benzothiadiazines; D001682:Biological Availability; D002192:Canrenone / Q000493:pharmacokinetics; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D013148:Spironolactone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D013449:Sulfonamides / Q000493:pharmacokinetics*
chemical_list: D000959:Antihypertensive Agents; D001581:Benzothiadiazines; D004338:Drug Combinations; D013449:Sulfonamides; D013148:Spironolactone; C046564:7-thiomethylspirolactone; D002192:Canrenone; C006480:althiazide
vernacular_title: Pharmacocinétique chez le sujet sain de l'altizide et de la spironolactone en association fixe pour deux posologies.