ABSTRACT
BACKGROUND: Cefcapene pivoxil hydrochloride (CFPN-PI) is an oral ester cephalosporin antibiotic with a broad spectrum. In this study, we investigated the pharmacokinetics (PK) and tolerability of CFPN-PI following single oral administration in healthy Korean subjects. METHODS: An open label, dose escalation, parallel group study was conducted in 18 healthy male volunteers. A single dose of CFPN-PI was administered to 6 subjects in each treatment group of 100, 150 and 200 mg. Serial blood and urine samples were collected up to 12 h and 24 h after dosing, respectively. Plasma and urine concentrations of cefcapene were measured by HPLC-UV. PK parameters were estimated using non-compartmental analysis. For the safety evaluation, adverse event monitoring, clinical laboratory tests and physical examination were performed throughout the study. RESULTS: Median values of time to peak plasma concentration were observed around 1.5 to 2.0 h. Maximum plasma concentrations (Cmax) were 1.04 +/- 0.22, 1.24 +/- 0.46 and 1.56 +/- 0.43 mg/L (mean +/- SD), and area under the plasma concentration time curve (AUCinf) were 2.94 +/- 0.46, 3.97 +/- 1.28 and 4.70 +/- 1.19 h*mg/L in 100, 150 and 200 mg dose groups, respectively. The differences of dose normalized Cmax and AUCinf among three groups were not statistically significant. The fractions of drug excreted in urine unchanged were 31.5 % - 42.9 %. There were no serious adverse events or clinically significant abnormalities related to CFPN-PI. CONCLUSION: CFPN-PI was well tolerated with single oral administration and showed a linear PK property within 100 - 200 mg in healthy Korean male subjects.
Subject(s)
Humans , Male , Administration, Oral , Pharmacokinetics , Physical Examination , PlasmaABSTRACT
BACKGROUND: Eplerenone is a selective mineralocorticoid receptor antagonist which effectively blocks mineralocorticoid receptors in various tissues throughout the body. The addition of eplerenone to optimal medical therapy reduces morbidity and mortality among patients post acute myocardial infarction complicated by left ventricular dysfunction and heart failure. The aim of this study was to evaluate pharmacokinetic characteristics and tolerability after multiple oral administration of eplerenone 100 mg for 7 days in healthy Korean volunteers. METHODS: A double-blind, randomized, placebo-controlled, parallel study was conducted in 22 healthy Korean subjects. Healthy males and females between age of 20 and 55 years were enrolled. Each subject received 100 mg eplerenone (N=16) or placebo (N=6) for 7 days. Blood samples for pharmacokinetic parameter determination on day 7 were collected pre-dose and up to 36 hours after last drug administration. Adverse events were reported throughout the treatment period. RESULTS: The steady-state concentration of eplerenone reached after multiple administration of eplerenone 100 mg for 7 days. The mean eplerenone Cmax of 1620.1 ng/mL was obtained at 1.0 hour (range 0.5 to 2 hours). The mean AUC0-24h,ss at day 7 was 8763.6 ng/mL*h. The mean oral clearance and mean terminal half-life of eplerenone were 13.0 L/h and 3.4 hours. There were some drug-related mild adverse events after eplerenone administration, but all adverse events recovered without any treatment. CONCLUSION: In this study, the pharmacokinetic parameters after multiple oral doses of eplerenone 100 mg for 7 days were evaluated and eplerenone at these doses were well tolerated in healthy Korean subjects.