[Pharmacokinetics of n-(5-oxynicotinoyl)-L-glutamic acid calcium salt upon bolus administration in rats and rabbits: interspecies extrapolation].

The pharmacokinetics of N-(5-oxynicotinoyl)-L-glutamate (ONG) was studied in rats (doses, 20, 100 and 500 mg/kg) and rabbits (50 mg/kg) after bolus administration of calcium salt of N-(5-oxynicotinoyl)-L-glutamic acid (Ampasse preparation). The ONG concentration in the blood serum was determined by HPLC assay with fluorimetric detection. The lower limit of accurate detection for ONG was 100 ng/ml. The ONG pharmacokinetics in rats was linear at relatively small doses (20-100 mg/kg) but nonlinear at a large dose (500 mg/kg). The ONG concentration decay had a two-phase character in both rats and rabbits, so that the pharmacokinetic profiles were fitted to a biexponential equation of the two-compartment model. Systemic pharmacokinetic parameters determined in rats and rabbits, respectively, were as follows: total clearance, 18 and 15 ml/(min kg); steady state distribution volume, 330 and 880 ml/kg; mean retention time, 0.3 and 1.0 h; half-life, 0.73 and 2.3 h. Using the allometric approach to the interspecies extrapolation of the pharmacokinetic data, the half-life of ONG in humans is predicted to be 4 h.

[Isolation of highly active strain producing the antistaphylococcal antibiotic batumin]. / Poluchenie vysokoaktivnogo shtamma--produtsenta antistafilokokkovogo antibiotika batumina.

The use of chemical and UV-induced mutageneses allowed us to increase the biosynthetic activity of the strain capable of producing new antistaphylococcal antibiotic, batumin. The strain of Pseudomonas batumici N17 producing 87-100 mg batumin per liter culture liquid was selected. Its activity was 3.5-5 times higher than the activity of the most potent natural strain. P. batumici N17 was shown to be stable in relation to the synthesis of batumin.

[Structure of the reaction adduct of xanthothricin with acetone]. / Stroenie addukta reaktsii ksantotritsina s atsetonom.

Reaction of xanthothricin demethylation by amines in acetone as a solvent yielded a new compound with a formula of C10H13N5O3. Mass spectrometry, 1H NMR-spectroscopy and x-ray analysis showed that the compound was 4H-1,6-dimethyl-4a(2-oxopropyl)-pyrimido-[5,4-e]-1 ,2,4-triazine-5,7-dione.

The antistaphylococcal pharmacodynamics of linezolid alone and in combination with doxycycline in an in vitro dynamic model.

To delineate the possible advantages of linezolid/doxycycline combinations over either drug alone, the in vitro pharmacodynamics of linezolid, doxycycline and linezolid plus doxycycline were studied with Staphylococcus aureus.S. aureus ATCC 43300 and a clinical isolate S. aureus 479 were exposed to twice-daily linezolid and once-daily doxycycline, alone and in combination, for five consecutive days. Three dosing regimens were simulated with each drug alone: linezolid (AUC(24)/MIC 30, 60 and 200 h-L30, L60 and L200, respectively) and doxycycline (AUC(24)/MIC 90, 180 and 520 h - D90, D180 and D520, respectively) and in combination: linezolid plus doxycycline (L30+D90; L60+D180 and L200+D520).With both S. aureus ATCC 43300 and S. aureus 479 exposed to linezolid or doxycycline, the area between the line crossing each time-kill curve at the level of 10(8) CFU/mL and the respective time-kill curve (I(E)) increased with increasing simulated AUC(24)/MIC ratios. Each of the combined treatments produced greater I(E)s than the sum of linezolid and doxycycline I(E)s observed in the respective single drug treatments.This study suggests that linezolid combinations with doxycycline may be synergistic in treating staphylococcal infections.