Showing papers on "Ribostamycin published in 1992"
TL;DR: A variety of aminoglycoside antibiotics mimic the effects of Ca2+ and other polyvalent cations on parathyroid function, with a 5- to 6-fold increase in potency for each additional amino group between four and six.
Abstract: We previously showed that the polycationic aminoglycoside antibiotic neomycin mimics the effects of high extracellular calcium (Ca2+) concentrations on several aspects of parathyroid function. In the present studies we examined the actions of several additional aminoglycosides on dispersed bovine parathyroid cells to investigate the relationship between antibiotic structure and function in eliciting Ca(2+)-like effects on intracellular second messengers and PTH release. Of the antibiotics tested, those with six amino groups (neomycin-B and -C) were most potent in inhibiting dopamine-stimulated cAMP accumulation, showing IC50 values (the concentration producing a half-maximal inhibitory effect) of 7.7 x 10(-5) and 1.5 x 10(-4) M. Gentamicin-C, paromomycin, and tobramycin, which have five amino groups, were less potent, with IC50 values of 4 x 10(-4), 10(-3), and 3.3 x 10(-4) M, respectively, while gentamicin-B, kanamycin, and ribostamycin, with four amino groups, were least potent (respective IC50 values, ...
23 citations
TL;DR: In order to test the biological importance of amino acids in the C-terminal quarter of aminoglycoside 3'-phosphotransferase II, seven of the highly conserved residues in this region were changed via site-directed mutagenesis and caused severe conformational distortions at the corresponding regions of the protein.
18 citations
Patent•
17 Feb 1992
TL;DR: In this article, a compound shown by formula I to formula II (R is morpholinomethyl, 4-amino-2-hydroxyalkanoylaminomethsyl or group showed by formula III; R is H, 1-18C saturated or unsaturated hydrocarbon chain containing acyl or prolyl; R and R are H or salicylidene).
Abstract: NEW MATERIAL:A compound shown by formula I to formula II (R is morpholinomethyl, 4-amino-2-hydroxyalkanoylaminomethyl or group shown by formula III; R is H, 1-18C saturated or unsaturated hydrocarbon chain- containing acyl or prolyl; R and R are H or salicylidene). EXAMPLE:5''-Deoxy-5''-morpholinoribostamycin. USE:An antifungal agent, an antimycotic agent and an antitumor agent. PREPARATION:Ribostamycin sulfate is used as a starting substance, an amino group thereof is protected with t-butoxycarbonyl group (BOC), OH at the 2- and the 3-position of neamine and at the 2- and the 3-position of ribose are protected with cyclohexylidene, respectively and the resulting substance is reacted with tosyl chloride to give a compound shown by formula IV. Then, this compound is reacted with sodium azide, the reaction product is catalytically reduced to give a compound shown by formula V. Further this compound is reacted with oxydiacetaldehyde and deprotected to give a compound shown by formula VI among compounds shown by formula I.
6 citations
TL;DR: Pharmacokinetic parameters for infants and children were compared with those observed in adults, and it was found that ribostamycin absorption and elimination were more rapid in the paediatric patients, and the Cmax in children and infants after intramuscular ribostammycin 10 mg/kg approached that in adults after an intramuuscular dose of ribost amycin 500mg.
Abstract: In the present study, ribostamycin concentrations in serum were measured by microbiological assay in 20 paediatric patients aged 3 months to 11 years after intramuscular ribostamycin 10, 15 and 20 mg/kg. All pharmacokinetic parameters and statistical analyses were calculated by computer. These results showed that the absorption rate constant (ka), elimination rate constant (ke), time to peak serum concentration (tmax), elimination half-life (t½), apparent volume of distribution (Vd/F), total body clearance (CL) and area under the serum concentration-time curve (AUC) were significantly different in infants under 6 months from those in children over 3 years (p 0.05]. The absorption of ribostamycin in infants was more rapid than that in children, but elimination was slower (p < 0.05). The Vd/F and CL in infants were also larger than in children (p < 0.01). There were significant positive correlations between Cmax, AUC and ribostamycin dosage (p < 0.01). Pharmacokinetic parameters for infants and children were compared with those observed in adults, and it was found that ribostamycin absorption and elimination were more rapid in the paediatric patients. The Cmax in children and infants after intramuscular ribostamycin 10 mg/kg approached that in adults after an intramuscular dose of ribostamycin 500mg. Using a 1-compartment open pharmacokinetic model, the optimum intramuscular ribostamycin administration interval was estimated as 6.01 and 7.56h for children and infants, respectively, while the value was 8.5h in adults. When the drug was administered in multiple doses of 15 mg/kg intramuscularly every 8h, no accumulation occurred in children. It is suggested that ribostamycin be administered in intramuscular doses of 10 to 15 mg/kg twice daily in infants and 3 times daily in children, respectively.
3 citations