Pharmaceutical Chemistry Journal (v.41, #12)

Pharmacokinetics and bioavailability of the new drug protecor upon peroral administration in rabbits and beagle dogs by S. N. Ptitsina; V. I. Bobrov; L. N. Sernov; M. M. Borisov; I. Kh. Ivanova; I. I. Miroshnichenko (625-628).
A new high-performance liquid chromatographic method with ultraviolet detection has been used to determine the levels of the new cardiotropic drug protecor in the blood of animals (chincilla rabbits, 2.2 ± 0.2 kg; and beagle dogs, 10 ± 0.5 kg). The parameters of protecor pharmacokinetics and bioavailability upon peroral administration of protecor tablets have been determined. Rabbits showed effective absorption of the drug uupon peroral administration in a single dose (100 mg/kg) with a peak concentration in the plasma (C max= 41 µg/mL) reached within T max= 3 h followed by rapid removal of the drug from the organism with a half-elimination time T /12β=1.71 h. Peroral administration of protecor in a single dose (50 mg/kg) in beagle dogs was characterized by C max= 34.6 µg/mL, T max = 3 h, and T /12β=0.75 h. The bioavailability of protecor upon peroral administration was estimated at 90% (rabbits) and 80.7% (beagle dogs).

Polarographic study of sydnophen excretion from rat organism by A. P. Snyakin; A. S. Berlyand (629-630).
The urinary excretion of sydnophen from rat organism has been studied using a polarographic technique for the first time. It is shown that approximately one third of the introduced drug dose is excreted unchanged with urine within 24 h. The elimination rate constant (K el = 0.11 h−1) and half-elimination time (t 1/2 = 6.3 h) are indicative of a low rate of sydnophen removal from rat organism. The proposed polarographic technique has proven to be reliable and convenient and is recommended for studying the clinical pharmacokinetics of sydnophen.

Rapid evaluation of the functional activity of the hepatic monooxygenase system by V. G. Gorokhova; A. G. Gorokhov; E. E. Kuznetsova; A. A. Runovich (631-633).
A rapid method for evaluation of the functional activity of the monooxygenase system of the liver has been developed based on TLC determination of the antipyrine content in saliva. Advantages of the proposed TLC method are the simplicity of sample preparation for the analysis, economy, rapid processing, and reliability. The method can be used to assess the detoxifying function of liver under clinical and outpatient conditions.

Synthesis and antiarrhythmic activity of new biologically active potassium and magnesium donors by A. S. Berlyand; A. A. Prokopov; A. G. Mulyar; M. T. Gasanov (634-637).
A series of new biologically active substances have been synthesized on the basis of glutamic acid, pyridoxalphosphate, and glycerophosphate to serve as ligands for potassium, calcium, and magnesium donors. General procedures for the synthesis and physicochemical characterization of the synthesized compounds are described. The synthesized compounds showed high antiarrhythmic activity in tests on rats and rabbits. The most active compounds (glutamic acid salts) were comparable in activity with the reference drugs and panangin and asparcam.

4-(1H-Benzimidazol-1-ylmethyl)-and 4-(2-methyl-1H-benzimidazol-1-ylmethyl)phenyl-β-D-glucopyranosides have been synthesized by glycosylation of the corresponding phenols. The hemolytic activity of the synthesized compounds was studied on whole venous human donor blood at concentrations of 100, 200, and 300 µg/mL. It was established that the glycosides exhibit high biological activity and enter erythrocytes faster than do the initial phenols, which suggests that they are promising for the development of new drugs.

Nitric oxide inhibitor activity of 2-amino-2-thiazoline derivatives by A. A. Mandrugin; T. P. Trofimova; V. M. Fedoseev; S. Ya. Proskuryakov; L. I. Shtein; A. N. Proschin; A. N. Pushin (640-642).
A series of 2-amino-2-thiazoline derivatives have been synthesized and characterized with respect to NOS-inhibitor activity in vivo. It was established that the dimensions of the substituents in 2-N-mono-and 2-N,N-disubstituted 2-amino-2-thiazolines are not significant for the biological activity of the products.

Synthesis and antibacterial activity of N,N′-diaryl-2-aryl-6-hydroxy-6-methyl-4-oxocyclohexane-1,3-dicarboxamides by V. L. Gein; E. V. Levandovskaya; N. V. Nosova; N. V. Antonova; E. V. Voronina; M. I. Vakhrin; A. P. Krivenko (643-645).
A series of N,N′-diaryl-2-aryl-6-hydroxy-6-methyl-4-oxocyclohexane-1,3-dicarboxamides have been synthesized by the reaction of N-arylamides of acetoacetic acid with aromatic aldehydes in the presence of piperidine. The structures of the products were determined by IR, PMR, and mass spectroscopy. Data on the antimicrobial activity of the synthesized compounds are presented.

Synthesis of aliphatic amides of 2-(2(-cyanophenyl)benzoic acid by A. P. Stankjavicius; L. N. Yanusiene; D. P. Zablockaite; R. B. Pechura (646-647).
Morpholides and piperidides of 2-(2′-cyanophenyl)benzoic acid have been synthesized in high yield (60%) by reaction of O-arylsulfonates of 9,10-phenanthrenequinone monooxime with aliphatic bases (morpholine and piperidine). The substituents in the arylsulfonate do not significantly influence these reactions. The reaction with aniline leads to the formation of 9,10-phenanthrenequinone phenylhydrazone in 49% yield. It is established that O-acylates of 9,10-phenanthrenequinone monooxime do not react with piperidine.

Standardization of the quality of the parent substance of sorbitol and sorbitol syrup is described. Sorbitol syrup is intended for use in the production of medicines for children of younger age. Physicochemical characteristics of the food grade powder and chemically pure grade sorbitol have been studied. The technology of sorbitol syrup production is developed and the physicochemical and technological parameters of the product are determined. The repeatability of the refractometric and spectrophotometric techniques for the quantitative analysis of sorbitol in syrup has been checked. The microbiological cleanliness of the parent substance and sorbitol syrup has been estimated. Methods for the microbiological decontamination of the parent substance and sterilization of syrup are proposed.

Controlled release of antiseptic drug from poly(3-hydroxybutyrate)-based membranes. combination of diffusion and kinetic mechanisms by R. Yu. Kosenko; A. L. Iordanskii; V. S. Markin; G. Arthanarivaran; A. P. Bonartsev; G. A. Bonartseva (652-655).
A polymeric system based on biocompatible and biodegradable poly(3-hydroxybutyrate) (PHB) is proposed for controlled release of furacilin (Frc). The kinetics of Frc release from PHB membranes containing 0.5–5.0 wt% Frc into a model aqueous medium at 25°C have been studied using a UV spectroscopy technique. The drug release profiles present a combination of diffusion and kinetic components. The diffusion component of the release kinetics has been analyzed and the dependence of the diffusivity on the drug concentrations has been determined. The rate constant of the release kinetics depends on the Frc concentration and is related to the hydrolytic destruction of PHB. The PHB hydrolysis is most clearly demonstrated in long-term experiments (after the first week of drug release). The obtained results are useful for the development of new controlled drug delivery systems containing several drugs, which provide a combined action on tissues and organs of the organism.

A composition of acyclovir matrix tablets and the technology for their production using commercially available pharmaceutical equipment are developed. A composition of the homopolysaccharide guar and the heteropolysaccharide gellan, which synergistically swells in water, was used as the matrix. Model tablets in in vitro experiments confirmed that acyclovir is released evenly over 24 h.

Direct molding technology for the production of zolpidem tablets by S. V. Emshanova; N. I. Veselova; A. P. Zuev; N. P. Sadchikova (659-661).
Results of the selection of auxiliary components and the optimization of technology of 10-mg zolpidem tablets are presented. A direct molding technology of zolpidem tablets has been developed with allowance for the physicochemical and technological properties of the parent drug substance and auxiliary components.

The amount of protein bound per 1 mL of the perfluorocarbon (PFC) emulsion depends on the emulsifier composition and the particle size. A relationship between the amount of bound protein on the particle surface and the physicochemical parameters of the PFC emulsion interaction with the blood serum, which indirectly characterize the surface properties of the PFC particles, is established.

Developing analytical methods for the creation of the state reference sample of noopept by A. V. Gusev; L. N. Grushevskaya; O. B. Stepanenko; N. I. Avdyunina; B. M. Pyatin; V. P. Lezina; O. S. Anisimova (666-669).
The physicochemical properties of noopept, a new domestic original drug with nootropic action, have been studied with a view to developing analytical methods, establishing quality criteria for the parent drug substance, and creating the state reference sample (SRS). These methods will be included in a draft of the regulation on the SRS of noopept.

Quality control of teraphthal production. 1. Chemical composition by M. S. Goizman; E. V. Degterev; K. F. Turchin; A. P. Arzamastsev (670-675).
It is shown that the drug teraphthal should be considered as a mixture of the octasodium salt of cobalt(II) 2,3,9,10,16,17,23,24-octacarboxyphthalocyanine (OCPC) and its oxidation product (component A) with the octasodium salt of OCPC and products from the extensive destruction of a substance with a similar elemental composition (component B). The composition can be estimated quantitatively using (i) the results of elemental analysis (H, N, Co) and (ii) PMR in combination with measurement of the weight loss on drying.