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

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.

A Randomized, Double-blinded, Open Label Study of the Efficacy and Safety of Cefcapene Pivoxil and Amoxicillin, Clavulanate in Acute Presumed Bacterial Rhinosinusitis

OBJECTIVES: Currently established first line therapy of acute (presumed bacterial) rhinosinusitis (ARS) consists of 10 to 14 days of oral amoxicillin or cephalosporins. This study compared the clinical efficacy and tolerance of cefcapene pivoxil (CP) and amoxicillin-clavulanate (AMC) in patients with ARS. METHODS: A randomized, open labeled, double-blinded trial of ARS patients over 15 years of age was performed. Patients diagnosed with ARS received paranasal sinus X-rays and nasal endoscopies and 2 weeks of either CP (150 mg, 3 times/ day) or AMC (625 mg, amoxicillin 500 mg, 3 times/day). All patients revisited the clinic on days 7, 14, and 28 for evaluation of changes in symptoms, endoscopy, and monitoring of any adverse reactions. Demographics, clinical characteristics and drug efficacy were also compared between the two groups. RESULTS: Among the 60 initially enrolled patients (CP 30, AMC 30), 5 patients in the CP group and 6 in the AMC group were excluded due to poor compliance. There were no significant differences in demographic data including age, sex, initial signs and symptoms, endoscopic and X-ray findings between the two groups. Rates of improvement after 2 weeks were 96% and 95.8% in the CP and AMC group, respectively. Sinus symptoms were changed significantly after 2 and 4 weeks, however, there was no difference between groups (P=0.41). The most common adverse reaction was gastrointestinal complication, diarrhea occurred in 1 patient in the CP group and 6 in the AMC group (P=0.04). CONCLUSION: CP and AMC were both effective in treating ARS. The difference of treatment outcome was not found between the two groups, however, gastrointestinal complications were less prevalent in the CP group.

Efficacy of Cefcapene Pivoxil for Empirical Therapy of Acute Uncomplicated Cystitis / 감염과화학요법

BACKGROUND: A high prevalence of fluoroquinolone resistance among uropathogens has been observed in Korea. Since empirical antimicrobial therapy should be guided by the proportion of pathogens resistant to the chosen antibiotic, the limitation of fluoroquinolones as the first empirical choice for acute cystitis is noticed in the clinical setting. The present study was undertaken to determine the susceptibility profiles of urinary isolates to cefcapene pivoxil and assess the clinical efficacy in patients with acute uncomplicated cystitis. MATERIALS AND METHODS: The study was a prospective, open label, non-comparative, non-blinded trial. Ninety-two patients with acute, uncomplicated symptomatic cystitis from two hospitals were treated with cefcapene pivoxil 100 mg tid for 5 days and followed up for 2 weeks. RESULTS: Seventy-seven of the 92 patients were evaluated. Bacteriological eradication of initial pathogens was achieved in 97.4% by 2 weeks after therapy termination. Seventy-four of 77 (96.1%) patients were symptomatically cured or improved after completion of therapy. Drug related adverse experiences were seen in 8 patients. None necessitated cessation of therapy. No significant biochemical or hematological abnormalities occurred. CONCLUSION: These results demonstrate the clinical efficacy and safety of empirical 5-day cefcapene pivoxil for acute uncomplicated cystitis.

Efficacy of Cefcapene Pivoxil for Empirical Therapy of Acute Uncomplicated Cystitis / 감염과화학요법

BACKGROUND: A high prevalence of fluoroquinolone resistance among uropathogens has been observed in Korea. Since empirical antimicrobial therapy should be guided by the proportion of pathogens resistant to the chosen antibiotic, the limitation of fluoroquinolones as the first empirical choice for acute cystitis is noticed in the clinical setting. The present study was undertaken to determine the susceptibility profiles of urinary isolates to cefcapene pivoxil and assess the clinical efficacy in patients with acute uncomplicated cystitis. MATERIALS AND METHODS: The study was a prospective, open label, non-comparative, non-blinded trial. Ninety-two patients with acute, uncomplicated symptomatic cystitis from two hospitals were treated with cefcapene pivoxil 100 mg tid for 5 days and followed up for 2 weeks. RESULTS: Seventy-seven of the 92 patients were evaluated. Bacteriological eradication of initial pathogens was achieved in 97.4% by 2 weeks after therapy termination. Seventy-four of 77 (96.1%) patients were symptomatically cured or improved after completion of therapy. Drug related adverse experiences were seen in 8 patients. None necessitated cessation of therapy. No significant biochemical or hematological abnormalities occurred. CONCLUSION: These results demonstrate the clinical efficacy and safety of empirical 5-day cefcapene pivoxil for acute uncomplicated cystitis.

In vitro Antimicrobial Activity of Cefcapene against Clinical Isolates / 감염과화학요법

BACKGROUND: Cefcapene pivoxil hydrochloride is a new oral cephem which has a broad-spectrum activity with expanded potency against Gram-positive bacteria, including Staphylococcus aureus and Streptococcus, as well as Gram-negative bacteria. In this study, we examined the in vitro activity of cefcapene against recently isolated clinical specimens from patients in a tertiary hospital. MATERIALS AND METHODS: We tested the in vitro antimicrobial activities of cefcapene and other cephalosporins against 450 clinical isolates from of patients in Asan Medical Center. Minimal inhibitory concentrations (MICs) were determined by agar dilution method according to the recommendations of National Committee for Clinical Laboratory Standards. RESULTS: Compared with other cephalosporins (cefaclor, cefpodoxime, and cefixime), cefcapene had lower MIC distributions for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and methicillin-susceptible S. aureus. Cefcapene had variable activity against Enterobateriaceae. CONCLUSION: Cefcapene had excellent in vitro antimicrobial activities against common typical bacterial respiratory tract pathogens and methicillin-susceptible S. aureus. Cefcapene appears to be a promising agent for treatment of community-acquired respiratory tract infections and infections caused by methicillin-susceptible S. aureus.

In vitro Antimicrobial Activity of Cefcapene against Clinical Isolates / 감염과화학요법

BACKGROUND: Cefcapene pivoxil hydrochloride is a new oral cephem which has a broad-spectrum activity with expanded potency against Gram-positive bacteria, including Staphylococcus aureus and Streptococcus, as well as Gram-negative bacteria. In this study, we examined the in vitro activity of cefcapene against recently isolated clinical specimens from patients in a tertiary hospital. MATERIALS AND METHODS: We tested the in vitro antimicrobial activities of cefcapene and other cephalosporins against 450 clinical isolates from of patients in Asan Medical Center. Minimal inhibitory concentrations (MICs) were determined by agar dilution method according to the recommendations of National Committee for Clinical Laboratory Standards. RESULTS: Compared with other cephalosporins (cefaclor, cefpodoxime, and cefixime), cefcapene had lower MIC distributions for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and methicillin-susceptible S. aureus. Cefcapene had variable activity against Enterobateriaceae. CONCLUSION: Cefcapene had excellent in vitro antimicrobial activities against common typical bacterial respiratory tract pathogens and methicillin-susceptible S. aureus. Cefcapene appears to be a promising agent for treatment of community-acquired respiratory tract infections and infections caused by methicillin-susceptible S. aureus.