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PubMedDate not supplied

In vitro protein binding interaction studies involving cefixime.

Cefixime is a new oral cephalosporin currently undergoing clinical trials. Selected agents with the likelihood for coadministration with cefixime in man were examined for their influence on the in vitro binding of cefixime in pooled serum from dog, monkey, and man. Results from these experiments showed no significant change in cerfixime binding in any animal species studied or in man by acetaminophen, heparin, phenytoin, diazepam, ibuprofen or furosemide at their maximum reported therapeutic concentrations. In contrast, both salicylic acid and probenecid resulted in concentration-dependent increases in the free fraction of cefixime (up to 2.5-fold). These findings demonstrate the usefulness of in vitro protein binding screening procedures for studying potential drug interactions that are mediated, at least in part, by changes in the protein binding of a drug.

Animals↗
PubMed1987

Pharmacokinetics of cefixime after once-a-day and twice-a-day dosing to steady state.

The pharmacokinetics of cefixime (CL 284,635; FK027), a new orally active broad-spectrum cephalosporin, were determined in 26 healthy volunteers, after multiple 200-mg twice-a-day (group 1; N = 13) or 400-mg once-a-day (group 2; N = 13) dosing for 15 days. On study days 1, 8, and 15, mean peak serum concentrations (Cmax) were 1.67, 1.75, and 1.87 micrograms/mL, respectively, for group 1 and 2.76, 3.04, and 2.67, respectively, for group 2. Over the 15-day period, mean trough serum concentrations were, on average, 0.40 and 0.08 microgram/mL for groups 1 and 2, respectively. Comparison (ANOVA) of serum and urinary excretion pharmacokinetic parameters for cefixime on days 1, 8, and 15 found no significant (P greater than .05) differences for either group except for a small but significantly (P less than .05) earlier time to reach Cmax and higher renal clearance on days 8 and 15 in group 1. These differences, however, are not clinically significant. On study days 1, 8, and 15, mean Cmax and AUC0-tau values for Group 2 were about 1.5 to 2.2 time those for Group 1. Urinary excretion of cefixime accounted for 11.9 to 14.5% and 9.9 to 12.4% of the dose in groups 1 and 2, respectively, over the 15-day study. Overall, there was no accumulation of cefixime in serum or urine nor was there a reduction in serum concentrations of urinary amounts over the 15-day dosing period when the drug was given either as a 200-mg twice-a-day or 400-mg once-a-day dosing regimen.

Adult↗
PubMed2004

Comparative evaluation of cefpodoxime versus cefixime in children with lower respiratory tract infections.

OBJECTIVE: The emergence of penicillin and macrolide resistant strains, responsible for Acute Lower Respiratory Tract Infections in children has offered third generation cephalosporins the platform to perform. The aim of the present study was to evaluate two third generation oral cephalosporins for their empirical use in community acquired lower respiratory tract infections in pediatric patients. An assessment of the clinical cure and bacteriological eradication rates and an overall tolerability was made. METHODS: It was a prospective, open, comparative, multicentric study. 776 children (Mean age 10 years) with LRTIs were included and randomly allotted to two groups respectively. A total of 396 children were given cefpodoxime susp 5 mg/kg b.i.d. and 380 patients on cefixime 4 mg/kg b.i.d. for 10-14 days. RESULTS: At the end of therapy, the clinical success with cefpodoxime was 97% as against 86.8% with cefixime. Bacterial eradication was 93.4% with cefpodoxime and 82.9% with cefixime. CONCLUSION: Cefpodoxime has been found to be a well-tolerated and superior alternative to cefixime synergistically documenting the extended spectrum of activity.

Acute Disease↗
PubMedDate not supplied

Pharmacokinetic parameters and killing rates in serum of volunteers receiving amoxicillin, cefadroxil or cefixime alone or associated with niflumic acid or paracetamol.

Pharmacokinetic parameters and killing rates in serum of volunteers receiving amoxicillin, cefadroxil or cefixime alone or associated with niflumic acid or paracetamol were studied. Niflumic acid (250 mg) or analgesic and antipyretic drugs such as paracetamol (500 mg) are often combined with antibiotics to avoid inflammation and pain in acute ear, nose and throat diseases. Pharmacokinetic interactions between these two classes of drugs have been described in experimental models, and exceptionally in humans. The aim of the present investigation was to study the interactions of these two drugs with three antibiotics (amoxicillin 500 mg x 2, cefadroxil 500 mg x 2, cefixime 200 mg and one placebo capsule) on pharmacodynamic parameters and on rate of killing in the serum of six healthy volunteers receiving the antibiotic associated or not with the product in a randomized cross-over double-blind trial. The bacteria most often involved in sinusitis, bronchitis and otitis media (Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus) three target diseases for oral cephalosporins and amoxicillin, were chosen for bacteriological study. Blood samples were obtained at 0.25, 0.50, 1, 1.5, 2, 4, 6 and 12 h after oral administration of antibiotics alone or associated with the drugs. There was a wash-out period of at least 1 week between the eleven sequences. Antibiotics were measured by two methods: bioassay and high performance liquid chromatography (HPLC). All serum samples obtained at peak level, 4 and 6 h were tested for killing rate. Area under the time kill curve was calculated by the trapezoidal rule method and relative bioactivity in percent was defined as follows: (AUC control - AUC test)/AUC control x 100. No pharmacokinetic interaction was found in the AUC and T1/2 of the plasma concentrations of the antibiotics or associated with the drugs, regardless of dose, as determined by HPLC or microbiological assay. For these beta-lactam antibiotics killing rate was found to be time-dependent. Bactericidal activity was improved on H. influenzae when cefixime was associated with niflumic acid and became concentration-dependent. A significant concentration relation was also found with niflumic acid or paracetamol associated with cefixime on Strep. pneumoniae.

Acetaminophen↗
PubMed1989

Cefixime versus trimethoprim/sulfamethoxazole in treatment of patients with acute, uncomplicated lower urinary tract infections.

One hundred six patients with acute, uncomplicated lower urinary tract infections participated in a randomized study that compared cefixime (one 400-mg tablet once daily) with trimethoprim (160 mg)/sulfamethoxazole (800 mg) (one tablet every 12 hours). Two cefixime recipients and 3 patients given trimethoprim/sulfamethoxazole had courses that were not evaluable for efficacy. At five to nine days post-therapy, 98 percent of the patients in each treatment group had clinical cure and bacteriologic eradication. At four to six weeks post-therapy, 87 percent (34/39) of the cefixime-treated patients and 83 percent (33/40) of those given trimethoprim/sulfamethoxazole had clinical cure and 90 percent (35/39) and 93 percent (37/40) of the patients in the respective treatment groups had bacteriologic eradication. Adverse clinical experiences or changes in the results of laboratory tests were few. Thus, a once-daily dose of cefixime was as safe and as effective as a twice-daily regimen of trimethoprim/sulfamethoxazole.

Anti-Infective Agents, Urinary↗
PubMed1994

An experimental study of cefixime in the treatment of Streptococcus pneumoniae otitis media.

Previous studies using the chinchilla animal model demonstrated that the third generation cephalosporin cefixime (Suprax) with split dosing was as effective as ampicillin in sterilizing the middle ear cleft when infected with S. pneumoniae. In this investigator-blinded, randomized trial, a single daily dose of cefixime (8 mg/kg per day) performed as well as split dosing of cefixime (8 mg/kg every 8 h) and ampicillin (150 mg/kg every 8 h) in the time to sterilization of the middle ear cleft. No statistically significant differences were noted between groups in otoscopy or tympanometry. All antibiotic regimens performed better than saline control (P < 0.0001) with regard to time to sterilization of the middle ear cleft. The results of this study support the daily administration of cefixime as an effective agent for the treatment of otitis media due to its extended half-life and broad antibiotic spectrum.

Acoustic Impedance Tests↗
PubMedDate not supplied

Development of Neisseria gonorrhoeae in vitro susceptibility test methods for cefixime including quality control guidelines.

Cefixime was tested in a multilaboratory study to establish susceptibility testing interpretive criteria and quality control (QC) guidelines for Neisseria gonorrhoeae. Interpretive criteria were established by using triplicate testing of 102 representative gonococcal strains. Only a susceptible category was proposed for cefixime (greater than or equal to 31 mm and less than or equal to 0.25 micrograms/ml) because of very rare, resistant isolates. QC ranges [N. gonorrhoeae American Type Culture Collection (ATCC) 49226] were established using multiple GC agar lots, three disk lots, and a number of test replicates consistent with the National Committee for Clinical Laboratory Standards (NCCLS) M23-T guidelines. Cefixime was stable in GC agar medium for at least 21 days when stored at 2 degrees-5 degrees C. Oral third-generation cephalosporins, such as cefixime, appear to represent potentially useful clinical alternatives to parenteral drugs of the same class for single-dose therapy of gonorrhea.

Cefixime↗
PubMed2001

Pharmacodynamics of ceftriaxone and cefixime against community-acquired respiratory tract pathogens.

Over the last decade or so there has been a growing interest in routes of antimicrobial administration other than by the conventional intravenous route for institutionalized patients and for some outpatients. Both oral (PO) and intramuscular (IM) routes of administration are less costly than giving antimicrobial agents by vein (IV). In addition, fewer complications such as catheter-related sepsis and phlebitis are associated with non-IV routes of administration. Furthermore, a reduced-dosage, reduced-volume IM administration of ceftriaxone may provide a tolerable route of administration and equivalent bactericidal activities compared with higher dose IV ceftriaxone. The purpose of this study was to determine the time that the drug concentration remained in excess of the minimum inhibitory concentration (MIC) (T > MIC) and the duration of bactericidal activities of ceftriaxone one gram administered IV, ceftriaxone 250 mg given IM and cefixime 400 mg given orally against clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in adult volunteers. Single doses of each agent were administered and serum concentrations were collected over the standard dosing period of 24 h for all study regimens. Ceftriaxone, regardless of route of administration and dose, resulted in bactericidal activities and T > MIC for 100% of the dosing period for S. pneumoniae, H. influenzae, and M. catarrhalis. Cefixime maintained at least 50% T > MIC and bactericidal activity against both isolates each of H. influenzae and M. catarrhalis. Against both isolates of S. pneumoniae, cefixime achieved T > MIC for at least 50% of the dosing period, but did not maintain bactericidal activity. Reduced dose ceftriaxone given IM seems to be a viable alternative to ceftriaxone IV if the pathogen, susceptibility and infection site are known. Based on T > MIC exceeding 50% of the dosing interval, cefixime would be considered an effective alternative to IV therapy against common respiratory tract pathogens. Clinical studies need to be conducted to confirm these findings.

Administration, Oral↗
PubMed1987

Dose-dependent pharmacokinetics of a new oral cephalosporin, cefixime, in the dog.

Cefixime (CL 284,635; FK 027) is a new third-generation oral cephalosporin. To study dose-dependent pharmacokinetics of cefixime in dogs, two balanced four-way crossover studies were conducted. In the first study, oral doses of 50, 100, and 200 mg/kg and an intravenous dose of 50 mg/kg cefixime were administered. In the second study, oral doses of 6.25, 12.5, and 25 mg/kg and an intravenous dose of 12.5 mg/kg cefixime were administered to the same dogs. A period of 1 month separated the two studies. When the two intravenous doses were compared (i.e., 12.5 and 50 mg/kg), a twofold increase in clearance and volume of distribution was observed after the higher dose. The oral systemic bioavailability in the dose range 6.25-50 mg/kg was 55%. It decreased to 44% at 100 mg/kg and 27% at 200 mg/kg. The average peak serum concentrations ranged from 15.8 micrograms/ml at 6.25 mg/kg to 119 micrograms/ml at 200 mg/kg. Within this concentration range, the fraction of free drug in serum (unbound to proteins) increased from 7 to 25%. This concentration-dependent protein binding was primarily responsible for changes in total clearance, volume of distribution, and bioavailability of the drug in dogs.

Administration, Oral↗
PubMed1993

Role of intrahepatic protein binding in the hepatobiliary extraction profile of cefixime in humans.

The hepatobiliary extraction profile of cefixime, a dianionic cephalosporin antibiotic, was studied in 10 patients, each of whom was provided with T-tube drainage of his or her common bile duct after cholecystectomy. After a single 200 mg oral dose, cefixime biliary clearance proved to be nonlinear, mostly in its initial phase, which is consistent with a concentrative uptake and intracellular protein binding for the drug. The latter process appears to be saturable and to operate at a rate that correlates with the total amount of cefixime recovered in the 24-hour bile drainage. Such findings seem to confirm the significant role played in vivo by hepatic ligandin in the hepatobiliary extraction of organic anions. The data also show that a single 200 mg oral dose of cefixime yields drug levels in bile substantially higher than the minimal inhibitory concentrations for the most frequent Enterobacteriaceae in biliary tract infections. Accordingly, this cephalosporin could be an interesting alternative in both prophylaxis and treatment of biliary tract infections.

Bile↗
PubMed1996

A comparison of ciprofloxacin, norfloxacin, ofloxacin, azithromycin and cefixime examined by observational cohort studies.

1. The safety in everyday clinical usage of three 4-quinolone antibiotics, (ciprofloxacin, norfloxacin and ofloxacin), was compared with similar data for azithromycin and cefixime, each agent being examined by Prescription-Event Monitoring (PEM) during the early post-marketing period. 2. In PEM the exposure data are derived from general practitioner prescriptions confidentially provided by the Prescription Pricing Authority. Outcome data are provided by questionnaires (green forms) on which the prescribing medical practitioner records event data. When necessary, further information is obtained from a number of sources which include follow-up of all pregnancies and the patients' life-time medical record. 3. The main outcome measures were demographic information, including the patient's date of birth and sex; the indication for prescribing the drug being monitored; the reason for stopping treatment; the start and stop dates of treatment and the events recorded during and after treatment. 4. The final cohort for each of the five antibiotics exceeded 11000 patients. The only event significantly related to the use of all five antibiotics was nausea/vomiting. This was also the most frequent adverse event causing treatment to be discontinued with norfloxacin, ofloxacin and azithromycin (relevant information was not requested in the studies of ciprofloxacin and cefixime). Vaginal candidiasis was significantly more frequently associated with the use of the three 4-quinolones than with azithromycin and cefixime but it was frequently delayed until the week or two after the cessation of therapy. Within each event, as recorded in these studies, the highest event rates (the number of events per 1000 patients) in the week following the start of therapy were: 9.2 for diarrhoea with cefixime; 4.9 for nausea/vomiting with ofloxacin; 2.4 for rash with azithromycin; 2.2 for abdominal pain with norfloxacin; 1.5 for headache/migraine with ofloxacin; 1.4 for malaise/lassitude with ofloxacin; 1.2 for dizziness with norfloxacin. Uncommon events (reported in less than 1:1000 patients) included rare cases of allergic phenomena, convulsions and pseudomembranous colitis. There were no reports of tendinitis, tenosynovitis or tendon rupture in children but tendon disorders were reported in the two months following the start of treatment in 20 adults. A total of 307 pregnancies were reported. Thirty-eight of the 55 women who received these drugs during the first trimester of pregnancy gave birth to healthy babies. No congenital abnormalities were reported. Apart from one case of unconfirmed pseudomembranous colitis, none of the other 2468 deaths that occurred in these studies was attributed to the antibiotics. 5. These five antibiotics are acceptably safe antimicrobial agents when used in general medical practice. PEM is an effective method for monitoring the safety of recently introduced antimicrobial agents.

Adult↗
PubMedDate not supplied

[Effectiveness and tolerance of cefixime in bacterial urinary tract infections in patients with myelomeningocele].

28 myelomeningocele patients (aged 2-30 years) with clinical symptoms of acute UTI participated in this open uncontrolled clinical trial at the Orthopedic University Hospital of Heidelberg (Dir.: Prof. Dr. H. Cotta). 4 patients were treated with 200 mg cefixime tablets bid, 24 patients received 4 mg/kg body weight cefixime suspension bid, according to age and weight of the patients. The duration of treatment was 6-10 days. Clinical and microbiological examinations were carried out before therapy as well as 1 day and 5 to 9 days after the end of treatment. The data of 25 patients could be evaluated for bacteriological and clinical efficacy. 5-9 days after treatment in 22 patients (88%) complete recovery was stated. In 3 patients a reinfection occurred. In 24 patients (96%) the baseline pathogens were eliminated under cefixime therapy. 5-9 days after the end of treatment in 3 patients reinfection was observed. Clinical side effects could be detected in 1 patient (vomiting). These results indicate that the oral cephalosporin cefixime is efficient and well tolerated in complicated UTI of myelomeningocele patients.

Adolescent↗
PubMed1992

Single-dose cefixime versus single-dose ceftriaxone in the treatment of antimicrobial-resistant Neisseria gonorrhoeae infection.

Sexually transmitted diseases (STDs) have a significant adverse effect on reproductive and child health worldwide. The control of STDs such as gonorrhea is therefore an absolute priority. Cefixime, an oral third-generation cephalosporin with in vitro activity similar to that of ceftriaxone, may be an effective candidate for the treatment of gonorrhea. The efficacy of a single oral 400-mg dose of cefixime was compared with that of a single intramuscular 250-mg dose of ceftriaxone for the treatment of Neisseria gonorrhoeae urethritis in 190 men and cervicitis in 46 women in Nairobi, Kenya. A bacteriologic cure was recorded in 100% of 63 evaluatable patients treated with ceftriaxone and 118 (98%) of 121 evaluatable patients treated with cefixime. Cefixime, as a single oral dose, is an effective alternative for the treatment of uncomplicated gonococcal urethritis in men and cervicitis in women.

Administration, Oral↗
PubMed1987

Noncomparative, open label, multicenter trial of cefixime for treatment of bacterial pharyngitis, cystitis and pneumonia in pediatric patients.

Cefixime, a new third generation oral cephalosporin antibiotic, was evaluated for safety and efficacy in the treatment of 206 children with acute bacterial pharyngitis, cystitis or pneumonia. Each patient had a throat, urine or sputum culture before therapy and was treated with a 10- to 14-day course of cefixime, 8 mg/kg once daily. Bacterial pathogens were isolated in 167 of 206 (81.1%). Streptococcus pyogenes (73.7% of isolates) and Escherichia coli (9.6%) were the most common Gram-positive and Gram-negative organisms, respectively. All patients were evaluable for safety, and 109 (52.9%) with pharyngitis (96) or cystitis (13) were evaluable for efficacy. Clinical failure occurred in 2 of 109 (1.8%) patients, both with pharyngitis; bacteriologic failure occurred in 1 patient with pharyngitis and 1 with cystitis. Five patients with pneumonia caused by possible pathogens also improved while taking cefixime. Drug-related adverse side effects occurred in 50 of 206 patients (24.3%); these were generally mild and led to discontinuing the antibiotic in only 4 patients (1.9%). The most common were diarrhea or loose stools (33 of 206, or 16%). Results of this study suggest that cefixime given once daily to children is safe and effective in the treatment of streptococcal pharyngitis and bacterial cystitis.

Adolescent↗
PubMed1993

Review of cefixime in the treatment of otitis media in infants and children.

During the past decade there has been an increase in the percentage of resistant bacteria isolated from middle-ear effusions aspirated from infants and children who have had acute otitis media. At least nine oral antibiotics or combination agents are available for this indication. Cefixime, a third generation cephalosporin, has excellent in vitro activity against both beta-lactamase-negative and beta-lactamase-positive Haemophilus influenzae and Moraxella catarrhalis, good activity against Streptococcus pneumoniae and Streptococcus pyogenes but relatively poor activity against Staphylococcus aureus. In children cefixime is similar in effectiveness to amoxicillin and cefaclor, but diarrhea and stool changes are more common with cefixime. Amoxicillin is still preferred for initial empiric treatment of uncomplicated acute otitis media. Its major drawback is limited efficacy when beta-lactamase-producing bacteria are the causative organisms. Cefixime is a viable alternative to amoxicillin for infants and children with acute otitis media when: (1) a beta-lactamase-producing H. influenzae or M. catarrhalis is isolated from otorrhea or tympanocentesis; (2) the child has a history of delayed hypersensitivity to the penicillins but no history of hypersensitivity to the cephalosporins; (3) there is a high incidence of resistant bacteria in the community; (4) there is not clinical improvement with amoxicillin; or (5) once daily administration is more convenient.

Animals↗
PubMed2000

Treatment of shigellosis with cefixime: two days vs. five days.

BACKGROUND: Although the recommended standard course of therapy for shigellosis is 5 days of oral ampicillin or trimethoprim-sulfamethoxazole therapy, successful outcome has been reported in adults treated with abbreviated courses of antibiotics. The purpose of this study was to compare short course (2-day) vs. 5-day therapy with cefixime for treatment of diarrheal disease caused by Shigella sonnei in children. METHODS: This was a prospective, randomized, double blind, placebo-controlled study. Patients were eligible if they were at least 6 months of age and presented to the Children's Hospital of Pittsburgh during an outbreak of diarrhea caused by S. sonnei, with (1) a history of fever and diarrhea (at least three loose or watery stools per day), (2) bloody diarrhea or (3) diarrhea and known exposure to an individual with documented shigellosis. Patients were randomized to receive either 2 days of cefixime (8 mg/kg(day) given once daily followed by 3 days of placebo or 5 days of cefixime. Telephone follow-up was performed on Days 3, 7 and 14 after enrollment. Follow-up stool cultures were obtained on Day 7 to assess bacteriologic cure. There were standardized definitions for cure, improvement, failure and relapse. RESULTS: Forty-seven patients were enrolled. Eleven were eliminated from analysis because their stool cultures were not positive for S. sonnei. There were 36 evaluable patients, 21 in the 2-day group and 15 in the 5-day group. Patients ranged in age from 6 months to 17 years. Forty-four percent of the subjects were male. Symptoms were improved or had resolved by Day 3 of therapy in all patients. There were 8 patients who experienced a clinical relapse: 5 of 21 (24%) patients in the 2-day treatment group and 3 of 15 (20%) in the 5-day group. There were 13 patients who experienced a bacteriologic failure (defined as the occurrence of a positive culture at the Day 7 follow-up visit), 11 of 20 (55%) in the 2-day group and 2 of 14 (14%) in the 5-day group (P < 0.02). CONCLUSION: Two- and 5-day treatment courses with cefixime for treatment of diarrheal disease caused by S. sonnei result in similar rates of clinical cure and clinical relapses; however, there was a higher rate of bacteriologic failure with shorter course therapy.

Cefixime↗
PubMed2001

Short term oral cefixime therapy for treatment of bacterial conjunctivitis.

BACKGROUND: There have been few controlled studies evaluating treatment of bacterial conjunctivitis beyond the newborn period. Topical therapy of bacterial conjunctivitis achieves a clinical cure but does not prevent acute otitis media (AOM). OBJECTIVES: The aim of this study was to compare systemic antibiotic therapy (cefixime) with topical therapy with polymyxin-bacitracin for treatment of acute bacterial conjunctivitis with regard to clinical and bacteriologic cure and prevention of AOM. METHODS: This study was a randomized, double blind, placebo-controlled trial of polymyxin-bacitracin ointment and oral placebo vs. topical placebo and oral cefixime in children with presumed acute bacterial conjunctivitis. Topical therapy was administered for 7 days; oral therapy was administered for 3 days. Bacterial cultures were obtained at entry and on Day 3 of treatment. Children were examined on Days 3 and 10 or if they worsened within 15 days of entry. RESULTS: Eighty children were enrolled in the study. Bacterial cultures of the conjunctiva were positive in 70% of children: Haemophilus influenzae (53.7%); Streptococcus pneumoniae (13.8%); H. influenzae and S. pneumoniae (1.2%); and Moraxella catarrhalis (1.3%). There were 7 (17.5%) bacteriologic failures among children receiving topical antibiotic and oral placebo and 15 (37.5%) bacteriologic failures among children receiving topical placebo and oral cefixime (P = 0.07 with Yates correction). There was no difference between study groups with regard to either clinical cure or the development of AOM. Nine children (11%), 5 who received active topical therapy and 4 who received active oral drug, developed AOM either during or within 15 days of study entry. CONCLUSION: Cefixime was not more effective than topical polymyxin-bacitracin in either the eradication of conjunctival colonization with respiratory pathogens or the prevention of AOM in children with acute bacterial conjunctivitis.

Acute Disease↗
PubMed1987

Saturable uptake of cefixime, a new oral cephalosporin without an alpha-amino group, by the rat intestine.

The mechanism of intestinal uptake of cefixime, a new oral cephalosporin antibiotic, has been examined using the everted jejunum of rats. The initial uptake rates were apparently pH-dependent with the maximum rate at pH 5.0 and a 3-fold reduction at pH 7.0. The uptake at pH 5.0 followed mixed-type kinetics involving saturable and non-saturable processes in a manner similar to that for several amino-beta-lactam antibiotics. Cefixime uptake was inhibited significantly by 20 mM permeants such as cyclacillin, cephradine, benzylpenicillin, propicillin, glycyl-L-proline and glycyl-glycine. Replacement of Na+ in the medium with choline produced a slight but significant inhibition of cefixime uptake. In spite of the absence of significant inhibition by the amino acids glycine and proline, the dipeptide, glycyl-L-proline in Na+-free medium showed a marked inhibitory effect. The inhibition kinetics of cefixime uptake by glycyl-L-proline and cyclacillin were consistent with competitive-type inhibition. This study provides the first evidence of saturable intestinal uptake of a cephem antibiotic without an alpha-amino group in the side chain, suggesting transport through the dipeptide carrier system(s).

Animals↗