Rapid determination of eplerenone in human plasma by LC-MS/MS and its application to pharmacokinetic study / 中国药学杂志

ABSTRACT

OBJECTIVE: To study the pharmacokinetics of single-and multiple-dose of eplerenone tablets in Chinese healthy volunteers. METHODS: Twelve volunteers were administered a single dose of eplerenone at 25, 50, and 100 mg according to 3 × 3 Latin square design. In multiple-dose study, 10 volunteers were administered eplerenone of 50 mg per day for 6 d. Eplerenone concentration in plasma was determined by LC-MS/MS. RESULTS: The main pharmacokinetic parameters of single-dose eplerenone of 25, 50 and 100 mg in 12 volunteers were as follows ρmax (450.2±146.2), (765.2±258.2), and (1262±428) μg·L-1, tmax (1.71±0.33), (2.06±1.01) and (2.79±1.48) h, t1/2(2.50±0.39), (2.69±0.55) and (2.84±0.53) h, AUC0-24h (2410±778), (4403±1522) and (8202±2398) μg·h·L-1, AUC0-∞ (2429±774), (4426±1523) and (8246±2407) μg·h·L-1. In the multiple-dose study, the main pharmacokinetic parameters after the first dose and those at steady state were as follows tmax (3.40±1.27) and (2.65±1.00) h, t1/2(3.03±0.66) and (3.22±0.62) h, ρmax (690.7±207.4) and (743.2±192.3), μg·L-1, ρSSmin(12.81±9.64) μg·L-1, ρavss (219.0±59.6) μg·L-1, and AUCSS (5256±1431) μg·h·L-1 CONCLUSION: The pharmacokinetics of eplerenone in human is linear in the range of 25-100 mg. There is no drug accumulation after multiple dosing. Copyright 2012 by the Chinese Pharmaceutical Association.