Pharmacokinetic Characteristics of Cefcapene Pivoxil Hydrochloride after Single Oral Administration in Healthy Korean Subjects

건강한 한국인 피험자에서 염산세프카펜 피복실 단회 경구투여 시 약동학적 특성에 관한 연구

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 ($C_{max}$) were $1.04{\pm}0.22$, $1.24{\pm}0.46$ and $1.56{\pm}0.43$ mg/L ($mean{\pm}SD$), and area under the plasma concentration time curve ($AUC_{inf}$) were $2.94{\pm}0.46$, $3.97{\pm}1.28$ and $4.70{\pm}1.19h{\times}mg/L$ in 100, 150 and 200 mg dose groups, respectively. The differences of dose normalized $C_{max}$ and $AUC_{inf}$ 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.