title: Bioequivalence assessment of two formulations of spironolactone in Chinese healthy male volunteers.
abstract: The bioavailability of a new spironolactone ((7alpha,17alpha)-7-(acetylthio)-17-hydroxy-3-oxopregn-4-ene-21-carboxylic acid gamma-lactone, CAS 52-01-7) formulation (test) was compared with a commercially available original formulation (reference) of the drug in 20 Chinese healthy male volunteers, aged between 21 and 27. The trial was designed as an open, randomized, single blind two-sequence, two-period crossover study. Under fasting conditions, each subject received a single oral dose of 100 mg spironolactone as a test or reference formulation with a 7-day washout period between the two formulations. The plasma concentrations of spironolactone and its active metabolite canrenone (CAS 976-71-6) were analyzed by a sensitive liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (LC-APCI-MS) method. The pharmacokinetic parameters included AUC(0.t), AUC(0-infinity), C(max), t1/2, and T(max). Values of AUC(0-t) demonstrate nearly identical bioavailability of spironolactone from the examined formulations. The AUC(0.12) of spironolactone was 148.35 +/- 39.5 and 144.39 +/- 53.02 ng x h/ml for the test and reference formulation, respectively. The AUC(0-60) of the metabolite canrenone was 1873.36 +/- 318.10 and 1911.28 +/- 355.60 ng h/ml for test and reference formulation, respectively. The maximum plasma concentration (C(max)) of spironolactone was 48.34 +/- 21.16 ng/ml for the test and 47.40 +/- 23.40 ng/ml for the reference product and the C(max) of the metabolite was 122.90 +/- 27.70 and 123.35 +/- 27.29 ng/ml for the test and reference product, respectively. No statistical differences were observed for C(max) and the area under the plasma concentration-time curve for both spironolactone and its active metabolite canrenone. 90% confidence limits calculated for C(max) and AUC from zero to infinity (AUC(0-infinity)) of spironolactone and its metabolite were included in the bioequivalence range (80%-125% for AUC). This study shows that the test formulation is bioequivalent to the reference formulation for spironolactone and its main active metabolite canrenone.
authors.affiliation: Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing, PR China.
authors.forename: Feng-Guo
authors.initials: FG
authors.lastname: Xu
authors.forename: Zun-Jian
authors.initials: ZJ
authors.lastname: Zhang
authors.forename: Hai-Juan
authors.initials: HJ
authors.lastname: Dong
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tian
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000328:Adult; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004232:Diuretics / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D013148:Spironolactone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013607:Tablets; D013810:Therapeutic Equivalency
chemical_list: D004232:Diuretics; D013607:Tablets; D013148:Spironolactone