Fosfomycin Sodium Research Articles

中耳腔に投与された薬剤の安全性について

A literature review of the safety or ototoxicity of antimicrobials applied to the middle ear cavity was performed. Animal experiments indicated ototoxic effects of otic drops used for the treatment of suppurative otitis media as well as some antiseptic solutions used for preoperative sterilization for the middle ear surgery. Clinical experience indicated fewer adverse effects following the use of antimicrobials and antiseptics in the middle ear cavity, although scant but serious side effects have been reported in the literature. The discrepancy of animal experiment and clinical experience is due largely to the anatomical differences of the cochlea, the round window of rodents are very thin and exposed into the middle ear cavity, whereas that of humans is thick and situated deep in the niche, and often covered with a pseudomembrane.We evaluated the safety of recently marketed eardrops Ofloxacin (OFLX) and Fosfomycin sodium (FOM). Based on the lack of reduction of the compound action potential in guinea pigs, we concluded that there was no ototoxic effect using OFLX or FOM.Also, the ototoxic effect of a Povidone-Iodine preparation was studied. Full strength solution instilled into the middle ear cavity did not cause sensorineural hearing loss at the 24 hours, indicating that rinsing the middle ear cavity with saline during surgery should prevent ototoxic effects of this product.

塩酸バンコマイシン投与患者の腎機能に及ぼす抗菌剤の影響

Abstract-Vancomycin hydrochloride (VCM) has a potent bactericidal activity against Gram positive bacteria, especially, Methicillin-resistant Staphylococcus aureus (MRSA). In the clinical situation, patients infected with not only with MRSA, but also with Gram negative bacterium or fungi are encountered. Because VCM has an adverse reaction of nephrotoxicity, we examined the nephrotoxicity and drug interactions of VCM and some antibiotics and antifungus agents in rabbits. We have already reported on the attenuation of nephrotoxicity by VCM with imipenem/cilastatin sodium, flomoxef sodium, fosfomycin sodium or minocycline hydrochloride, but no attenuation with ceftazidime, cefpimizole sodium or fluconazol. In this study, we investigated the renal function and VCM clearance in MRSA-infected patients, and compared our findings with those in the patients coadministered antimicrobial agents which decreased the nephrotoxicity of VCM in rabbits (decreasing group, n=23) and the patients coadministered the drugs which didn't decrease the nephrotoxicity in rabbits or administered VCM alone (non-decreasing group, n=22). No significant differences were observed regarding age, serum creatinine, BUN, serum potassium, total protein, albumin, WBC and CRP at the starting time of VCM-treatment, VCM doses, period of VCM treatment, and serum VCM concentrations (peak, trough) between the decreasing group and the non-decreasing group. However, the serum creatinine levels in the nondecreasing group were significantly higher than those of the decreasing group at 2 weeks after the VCM theatment. In addition, the serum creatinine levels at the end of the VCM treatment in the non-decreasing group were higher than those of the dereasing group.However, no significant differences were observed in the VCM clearance and BUN between the decreasing group and the non-decreasing group, even though the serum creatinine in the nondecreasing group significantly increased. The high ratio of cancer in our patients (decreasing group n=12, non-decreasing group n=15) may have influenced our resuls. Further investigations are needed to estimate whether or not antimicrobial agents may influence the renal functions in VCM administered patients.

A phase I study on Fosfomycin sodium (FOM) nasal solution by nebulization

A phase I study on Fosfomycin sodium (FOM) nasal solution by nebulization

A study of the absorption and excretion of fosfomycin sodium in children

Fosfomycin sodium (FOM-Na, Forocyle-S) was administered at 25 mg/kg or 50 mg/kg to 15 children between the ages of 3 and 15 through intravenous injection or through 1 hour intravenous drip infusion, and concentrations in blood serum and excretion through urine were examined and a pharmacokinetic analysis was carried out using the one-compartment model. 1. Average concentrations in the blood serum after injections with 25 mg/kg and 50 mg/kg were 55.3 +/- 6.3 micrograms/ml and 118.8 +/- 31.1 micrograms/kg 30 minutes after injection, respectively, and their half-lives were 1.04 +/- 0.15 hours and 0.98 +/- 0.17 hours, respectively. Six hours after injection, the levels were 2.7 +/- 1.6 micrograms/kg and 6.2 +/- 5.5 micrograms/kg, respectively. With 1 hour intravenous drip infusion of 25 mg/kg and 50 mg/kg, average concentrations the blood serum were 34.2 +/- 14.9 micrograms/ml and 89.7 +/- 6.7 micrograms/ml, respectively, and their half-lives were 0.87 +/- 0.24 hour and 0.69 +/- 0.10 hour, respectively. Six hours after the administration, the levels were 2.7 +/- 1.8 micrograms/ml and 6.7 +/- 0.8 micrograms/ml. There was a clear dose response in the concentration levels in the blood in those given the drug at 25 mg/kg and 50 mg/kg in either method of administration. 2. Average levels in urine after injection of 25 mg/kg and 50 mg/kg were 5,778 +/- 2,257 micrograms/ml and 6,268 +/- 3,329 micrograms/ml 0-2 hours after administration, respectively, and average levels at 4-6 hours were 701 +/- 765 micrograms/ml and 1,588 +/- 1,324 micrograms/ml, respectively. Average excretion, rates into the urine were 72.8 +/- 11.0 and 73.9 +/- 11.1%, respectively. In case of 1 hour drips infusion of 25 mg/kg and 50 mg/kg, average concentrations in the urine 0-2 hours after administration were 3,570 +/- 1,540 micrograms/ml and 11,800 micrograms/ml, respectively, and averages for 4-6 hours were 211 +/- 124 micrograms/ml and 1,300 micrograms/ml. Average rates of excretion into the urine for the first group was 57.9 +/- 16.3% and the second group was 78.4%. Clear dose response was observed in changes of drug concentration levels in the urine with 25 mg/kg and 50 mg/kg doses through either administration method, and in terms of excretion into the urine, no noticeable differences were observed between the different amounts administered or different administration methods.(ABSTRACT TRUNCATED AT 400 WORDS)

Transtympanic iontophoresis of dexamethasone and fosfomycin.

The effects of transtympanic iontophoresis of corticosteroids and antibiotics on otitis media with effusion (OME) were investigated. An experimental study using guinea pigs revealed that transtympanic passage of dexamethasone sodium phosphate and fosfomycin sodium by iontophoresis had sufficient anti-inflammatory and antimicrobial effects. Twenty children with OME (33 ears) who were treated by iontophoresis were compared with 28 untreated children with OME (35 ears) with respect to improvement assessed by tympanoaudiometry. After one month, tympanoaudiometry revealed improvement in 21 (63.6%) of the treated ears but in only 13 (37.1%) of the untreated ears, indicating the efficacy of this treatment for OME.

中耳局所投与剤としてのホスホマイシンの内耳に及ぼす影響 ゲンタマイシンとの比較成績

Antibiotics which have ototoxicity should be carefully administered in clinical treatment. Patients with chronic otitis media are often treated by intratympanic therapy. Basic studies on ototoxicity, however, are rarely reported.The present study was performed to examine the influence of intratympanic antibiotic administration on the internal ear in 46 guinea pigs (19 in the fosfomycin group, 17 in the gentamicin group, 10 in the physiological saline group as controls). Fosfomycin sodium solution of 0.2ml (6mg), gentamicin solution of 0.2ml (8mg) and physiological saline of 0.2ml were instilled daily into the tympanic cavity through a silicon tube at the back of the ear of the guinea pig for 10 days.Electrocochleography (ECoG) was performed to examine the ECoG-threshold in the experimental animals and scanning electronmicroscopy (SEM) was also used to observe the extirpated cochlea after sacrifice. The ototoxicity of gentamicin was observed both functionally and morphologically to almost the same degree. On the other hand no ototoxicity of fosfomycin was noted.The clinical significance and usefulness of topical administration into the tympanic cavity of these antibiotics are discussed briefly.

Basic and Clinical Studies on Fosfomycin Sodium Salt for Intravenous Injection in the Otorhinolarygologic Field

Basic and Clinical Studies on Fosfomycin Sodium Salt for Intravenous Injection in the Otorhinolarygologic Field