Cefoselis

We investigated the effect of infusion rate and experimental renal failure on the pharmacodynamics of cefoselis (CFSL)-induced seizures. As an animal model of CFSL-induced seizures, male Wistar rats received an intravenous infusion of CFSL at one of three different rates (1.4-5.8 g/h/rat) until the onset of maximal seizures (which occurred after 8.0 to 36.0 min of infusion). Samples of cerebrospinal fluid (CSF), blood (for serum), and brain were obtained immediately after stopping infusion of CSFL. The serum concentration of CFSL at the onset of seizures increased with increasing infusion rate, but brain and CSF concentrations of CFSL at the onset of seizures were not affected by the infusion rate. Ureter-ligated (UL) and control rats received an intravenous infusion of CFSL at 1.4 g/h/rat until the onset of seizures. Then the same procedure as used to determine the effect of infusion rate on the concentrations of CFSL was carried out. Renal failure was associated with a significant decrease in the amount of CFSL required to induce seizures.

Majocchi's granuloma (MG) is a rare deep skin dermatophyte infection that can occur either in immunocompetent or in immunocompromised individuals. Oral itraconazole or terbinafine is considered to be the first choice of treatment. We report an immunocompetent man with deep nodular form of MG, the form which is generally found in immunosuppressed individuals. Previous treatment with either oral itraconazole or terbinafine yielded no apparent improvement. After a series of examination, the man was diagnosed as having Trichophyton rubrum-induced MG mixed with bacterial infection as evidenced by growth of Klebsiella pneumoniae in tissue bacterial culture. The patient was treated with a combination of cefoselis and levofloxacin for bacterial clearance followed by voriconazole treatment. After approximately 4 months of voriconazole treatment, the lesions completely resolved. Alternative medicine (voriconazole) can be considered in case of refractory infections during MG treatment.

The action of the beta-lactam antibiotics, penicillin-G (PCG) and cefoselis (CFSL) on GABA(A) receptors (GABA(A)-R) was investigated using the two-electrode voltage clamp technique and Xenopus oocyte expressed murine GABA(A)-R. Murine GABA(A)-Rs were expressed in Xenopus oocytes by injecting cRNA that encoded for each subunit (alpha1, beta2, and gamma2) and the effects of PCG and CFSL on the alpha1beta2gamma2s subunit receptors were examined using two-electrode voltage clamp. Using the alpha1beta2gamma2s GABA(A)-R, PCG and CFSL inhibited GABA-induced currents in a concentration-dependent manner, with IC(50)s of 557.1+/-125.4 and 185.0+/-26.6 microM, respectively. The inhibitory action of PCG on GABA-induced currents was non-competitive whereas that of CFSL was competitive. Mutation of tyrosine to phenylalanine at position 256 in the beta2 subunit (beta2(Y256F)), which is reported to abolish the inhibitory effect of picrotoxin, drastically reduced the potency of PCG (IC(50)=28.

The process of degradation was studied by using an HPLC-DAD method. Two degradation products were identified with a hybrid ESI-Q-TOF mass spectrometer. The influence of temperature and relative air humidity (RH) on the stability of cefoselis sulfate was investigated. In the solid state at increased RH the degradation of cefoselis sulfate was an autocatalytic reaction of the first order with respect to substrate concentration while in dry air was first-order reaction depending on the substrate concentration. The kinetic and thermodynamic parameters of degradation were calculated.