Cefcapene Pivoxil Hydrochloride Research Articles

Assessment of the Safety of Exposure to Cefcapene Pivoxil during the First Trimester of Pregnancy: A Prospective Cohort Study in Japan.

Cefcapene pivoxil hydrochloride is an antibiotic often used by women who are or may be pregnant. However, the safety of exposure to it during the first trimester of pregnancy has not been assessed. In this study, we aimed to clarify the effects of exposure during the first trimester of pregnancy on maternal and fetal outcomes. Data were obtained from pregnant women who were counseled on drug use during pregnancy at two Japanese facilities from April 1988 to December 2017. The incidence of major malformations in singleton pregnancy was compared between neonates born to women who took cefcapene pivoxil hydrochloride (n = 270) and control drugs (n = 1594) during their first trimester. The adjusted odds ratio of the incidence of major malformations was calculated using multivariate logistic regression analysis adjusted for smoking during pregnancy and maternal age. The incidence of major malformations was 2.6% in the cefcapene pivoxil hydrochloride group and 1.8% in the control group. There were no significant differences in the incidence between the cefcapene pivoxil hydrochloride and control groups (adjusted odds ratio: 1.48 [95% confidence interval: 0.64-3.42], p = 0.36). This prospective cohort study showed that exposure to cefcapene pivoxil hydrochloride during the first trimester of pregnancy was not associated with increased risk of major malformations in infants. Our findings will help healthcare providers in choosing appropriate medicines.

Cefcapene pivoxil-induced hypocarnitinemic hypoglycemia in elderly man with subclinical ACTH deficiency: a case report

BackgroundDrug-induced hypocarnitinemia has been noted as a cause of hypoglycemia in children. However, adult cases are extremely rare and pre-existing conditions (including endocrine disorders and frailty) have been suggested to be involved. Hypoglycemia due to drug-induced hypocarnitinemia is quite rare, and there were few reports of pivoxil-containing cephalosporin (PCC)-induced hypocarnitinemia in adults.Case presentationWe present a case of an 87-year-old man with malnutrition, and frailty. He developed severe hypoglycemia with unconsciousness after taking cefcapene pivoxil hydrochloride, one of PCC, and hypocarnitinemia was diagnosed. Despite levocarnitine administration, asymptomatic mild hypoglycemia had persisted. Subsequent investigation revealed subclinical ACTH deficiency due to empty sella, which played a key role to maintain mild hypoglycemia as underlying disorder, and PCC-induced hypocarnitinemia triggered severe hypoglycemia. The patient responded to hydrocortisone therapy.ConclusionsWe need to be aware of the facts that PCC can induce severe hypocarnitinemic hypoglycemia in elderly adults associated with frailty, malnutrition, and subclinical ACTH syndrome.

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.

Determination of cefcapene acid by LC–MS and their application to a pharmacokinetic study in healthy Chinese volunteers

Simple, rapid and specific liquid chromatography–mass spectrometry (LC–MS) methods have been developed and validated for the quantification of cefcapene acid in human plasma and urine. Plasma samples were simply pretreated with methanol for deproteinization. Urine samples were briefly diluted with methanol–water (50:50, v/v), and centrifuged to remove large particles. Chromatographic separation was performed on a Hedera ODS-2 column. For the plasma assay, the isocratic mobile phase consisted of 35% solvent A (Methanol) and 65% solvent B (10mM ammonium acetate buffer solution containing 0.2% folic acid) with a flow rate of 0.3mL/min. For the urine assay, the isocratic mobile phase consisted of 30% solvent A (Methanol) and 70% solvent B (10mM ammonium acetate buffer solution containing 0.2% folic acid) with a flow rate of 0.3mL/min. The assays were linear over the concentration ranges of 0.03–5μg/mL in plasma and 0.1–400μg/mL in urine, and were successfully applied to a pharmacokinetic study after single and multiple oral administrations of cefcapene pivoxil hydrochloride tablets in healthy Chinese volunteers.

Concentration of cefcapene pivoxil hydrochloride (CFPN-PI, Flomox®) in serum and in synovial fluid of temporomandibular joint with temporomandibular joint disorder

Concentration of cefcapene pivoxil hydrochloride (CFPN-PI, Flomox®) in serum and in synovial fluid of temporomandibular joint with temporomandibular joint disorder

Efficacy of azithromycin administration in prevention of respiratory tract infection after bronchoscopic biopsy: A randomized, controlled trial

Respiratory tract infection is a serious complication associated with bronchoscopic biopsy. This study attempted to examine its incidence and determine an efficacious therapy for preventing such infections. Nine hundred and thirty patients who underwent bronchoscopic biopsy in Osaka City University Hospital outpatient clinic were enrolled in the study. All patients were randomly assigned to receive a 3-day course of azithromycin (500 mg/day), cefcapene pivoxil hydrochloride (300 mg/day) or no antibiotics. The primary outcome was the incidence of respiratory tract infection after bronchoscopic biopsy among the three groups. In the no-treatment group, nine of the 310 patients (2.9%) had respiratory tract infection after bronchoscopic biopsy. All patients with infection had abnormal bronchoscopic findings. Of the patients with respiratory tract infection, 60% were in the no-treatment group, 26.7% in the cefcapene group and 13.3% in the azithromycin group. Although not statistically significant, the incidence in the azithromycin group (0.7%) was lower than in the no-treatment group (P = 0.06). Among the patients with abnormal bronchoscopic findings, the incidence in the azithromycin group was significantly lower than that in the no-treatment group (3.0% vs. 14.8%; P = 0.02). Moreover, maximum C-reactive protein values also appeared to be lower in the azithromycin group than in the no-treatment group and the cefcapene group. A 3-day course of azithromycin administration is well tolerated and effective in preventing infection post bronchoscopy.

Clinical study of complicated urinary tract infection using ‘The UTI Criteria (Draft Fourth Edition)’: Measurement methods for pyuria

To evaluate the influences the change of the measurement method of pyuria from conventional centrifuged sediment to microchamber uncentrifuged urine for the results of evaluation of antimicrobial agents in clinical study against complicated urinary tract infections. From the viewpoint of international harmonization of judgement criteria, the recent method for counting white blood cells (WBC) in urine has changed from using uncentrifuged urine to using a microchamber in all countries. Targeted diseases were non-catheterized complicated urinary tract infection, and cefcapene pivoxil hydrochloride or levofloxacin were used as antimicrobial drug. Pyuria was examined using the counting chamber method, a quantitative method using uncentrifuged urine with a microchamber, and the sedimentation method. Overall clinical efficacy in early evaluation by the two methods in measuring pyuria was evaluated as different in eight patients (7.3%). It was rated excellent in 63 (52.9%), moderate in 32 patients (26.9%) and poor in 24 (20.2%) with an efficacy rate of 79.8% using the counting chamber method, and excellent in 68 (57.1%), moderate in 27 (22.7%) and poor in 24 (20.2%) with an efficacy rate of 79.8% using the conventional sedimentation method No significant difference was seen between the two methods of WBC count in urine.

消化管用薬によるＣｅｆｃａｐｅｎｅ‐Ｐｉｖｏｘｉｌ Ｈｙｄｒｏｃｈｌｏｒｉｄｅの吸収性への影響

The effects of concomitant gastrointestinal drugs on the absorptivity of cefcapene-pivoxil hydrochloride (CFPN-PI) were examined in patients who were hospitalized due to infection and were to be treated with a gastrointestinal drug. CFPN-PI was orally administrated at a dose of 100mg after meals concomitant with a gastrointestinal drug. The urinary recovery rate of CFPN was determined from the urine collected for 12 hours after the first administration of CFPN-PI. In addition, the clinical efficacy and safety of CFPNPI was evaluated. The results were as follows:1. The mean urinary recovery rate of CFPN in 25 cases evaluable for the absorptivity of CFPN-PI was 24.7% (95% confidence interval: 21.0-28.3%). The mean urinary recovery rate of CFPN was 25 .6% in the famotidine group, 23.9% in the dried alminium hydrooxide gel group, and 25.2% in the teprenone group.Thus, there was no significant difference in the urinary recovery rate of CFPN among the concomitant drug groups (p-value: 0.9239).2. Clinical efficacy was judged as “excellent” in 4 cases, “good” in 16 cases, and “poor” in 2 cases, generating a clinical efficacy rate of 90.9%.3. The incidence of adverse drug reactions (ADRs) was 16.7%. All of the ADRs were slight in severity and were resolved without any treatment.Based on these results, it is suggested that the concomitant administration of the gastrointestinal drugs used in this study does not largely affect the absorptivity of CFPN-PI and the drug shows a sufficient antibacterial effect at the approved dose in such concomitant administration.

Gas-Forming Primary Psoas Abscess Caused by Klebsiella pneumoniae

Gas-Forming Primary Psoas Abscess Caused by Klebsiella pneumoniae

Absorption of ester prodrugs in Caco-2 and rat intestine models.

The aim of this study was to elucidate the absorption mechanism in Caco-2 and rat intestine models in order to improve the accuracy of prediction of oral absorption of ester prodrugs. Pivampicillin and cefcapene pivoxil hydrochloride (CFPN-PI), ester-type oral antibiotics, were chosen as model ester prodrugs. The level of esterase activity in Caco-2 cells was lower than that measured in the rat jejunum when p-nitrophenyl acetate was used as a substrate. Almost complete ester hydrolysis occurred before the ester prodrugs reached the basolateral side of the monolayer, and the disappearance of prodrugs was thought to be due to metabolism or transport after addition to the apical side of the monolayer. When pivampicillin and CFPN-PI were used, the amounts of ampicillin and cefcapene (CFPN) produced by hydrolysis of prodrugs were increased because intracellular degradation of prodrugs resulted in intracellular accumulation. On the other hand, when ampicillin or CFPN was used, only a small amount of the drug reached the basolateral side of the monolayers and no intracellular accumulation was observed. The permeability of CFPN-PI, the solubility of which is dependent on the acidity of gastric juice, across a Caco-2 monolayer or rat intestine, was also investigated by using an in vitro system that mimics the physiological state of the human gastrointestinal tract. The oral absorption of CFPN-PI in humans is predicted to be good either in the Caco-2 model or in the rat intestine model. It is concluded that our system may be a valuable tool for evaluation of oral absorption of ester prodrugs metabolized during permeation through the intestinal epithelium. Broader evaluation of such a system is warranted.

Study of the absorption of cefcapene pivoxil in patients with infectious disease and soft stool or diarrhea

Cefcapene pivoxil hydrochloride (CFPN-PI), an ester cephem antibiotic, was orally given at a dose of 100 mg three times daily in patients with infection and soft stool or diarrhea, and its absorption was determined using the recovery ratio of 12-h urine pooled after the initial administration as an index. The primary endpoint, the recovery ratio of 12-h urine pooled after oral administration, could be evaluated in six of the eight patients finally gathered, and the mean value was 30.1 +/- 5.8%, which was not considered to differ from the mean value of 34.4 +/- 5.5% obtained in six healthy adult volunteers in the previous phase I study. Clinical efficacy in the eight patients was rated as very effective, effective, and ineffective in two, five, and one patients, respectively, with an effective ratio of 87.5% (7/8). Neither adverse drug reactions nor abnormal laboratory data were observed in any patient. These results indicate that CFPN-PI, at the routine oral dose, does not cause any problems in terms of absorption, efficacy, and safety when it is used in patients with infection and soft stool or diarrhea.

High-level expression, purification, and some properties of a recombinant cephalosporin-C deacetylase

To maximize the expression of the cephalosporin-C deacetylase (CAH) gene isolated from Bacillus subtilis SHS 0133 in Escherichia coli, a series of expression plasmids was constructed with various spacings between the Shine-Dalgarno sequence and the ATG initiation codon. As the most efficient expression plasmid, we selected pCAH431, which has the trp promoter, a replication origin derived from pAT153, and a spacing of 13 nucleotides. E. coli JM103 with pCAH431 produced 4.9 g of CAH per liter on cultivation at 37°C for 20 h in a 30- l jar fermentor. Since the amount of CAH reached about 70% of the total protein in the soluble fraction of the cells, and CAH was recovered from the cell extracts in an active form, the CAH was purified easily to homogeneity by only one column chromatography step. Twenty grams of 7-aminocephalosporanic acid was completely converted to deacetyl-7-aminocephalosporanic acid, a starting material for cefcapene pivoxil hydrochloride, by 12 mg of the purified enzyme without significant appearance of by-products. Thus, our expression and purification system has made the industrial production of CAH possible.