Biotransformation and pharmacokinetics of gidazepam in rats

Колыванов, Г. Б.; Zherdev, V. P.; Rodionov, A. P.; Litvin, A. A.; Otabekova, S.G.

doi:10.1007/bf00772848

Cited by 1 publication

(6 citation statements)

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Section: Experimental Chemical Partmentioning

confidence: 99%

Section: Experimental Chemical Partmentioning

confidence: 99%

“…Each experimental point was determined by averaging data obtained for 6 -8 animals. The concentrations of drugs and their metabolites were determined by HPLC as described in [4].…”

Section: Experimental Biological Partmentioning

confidence: 99%

“…The membrane separating the donor and acceptor chambers was made of poly(vinyl acetate) and impregnated with lipids (fatty alcohols and fatty acids). Depending on the combination of impregnating lipid components, it was possible to simulate membranes of the stomach and intestinal walls [2].(c) Determining the lipophilicity constants (log K w ) of drugs. The characteristics of lipophilicity were determined by reverse-phase HPLC on a 4.6´250 mm column with 583 0091-150X/04/3811-0583…”

mentioning

confidence: 99%

“…The drug concentration in the samples was determined by UV spectrophotometry. The drug dissolution process was described in terms of the first-order kinetic equation, and the K sol values were determined by least squares [2].(b) Determining the diffusion rate constants (K d ) of drugs. The diffusion constants were determined using a membrane model simulator of the Sartorius 16750SM type (Germany).…”

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confidence: 99%

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Relationship between physicochemical characteristics and pharmacokinetic parameters of 1,4-benzodiazepine derivatives

et al. 2004

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A rational targeted search for new effective drugs of the benzodiazepine group should be based on established relationships between the physicochemical properties of compounds and their pharmacological activity, the direction and rate of biotransformation, and the pharmacokinetic parameters [1]. Correlations between these factors make possible drawing reliable judgments about the rate of absorption from the gastrointestinal tract, the time of attaining maximum concentration in the blood, the time of circulation in the organism, and the rates of accumulation and elimination of new drugs, based on the results of analysis of the known data for analogous substances.This aim of this study was to determine some important physicochemical characteristics (dissolution rate constant, diffusion rate constant, lipophilicity constant) of a series of 1,4-benzodiazepine derivatives and to establish relationships between these values and the parameters of pharmacokinetics of these compounds in rats. EXPERIMENTAL CHEMICAL PARTThe study was performed on a series of 1,4-benzodiazepine derivatives with structures differing from each other in the nature of the chemical radicals at the N 1 , C 3 , and C 7 positions of the benzodiazepine cycle and the C 2 position of the phenyl ring (Table 1).(a) Determining the dissolution rate constants (K sol ) of drugs. The measurements were performed for fractions of the parent substances with a particle size not exceeding 0.2 mm, which were separated by sieving powdered compounds through a standard silk sieve No. 31. A sol-free filter with a weighed amount of the powdered drug was placed in a dry basket. The basket was immersed into a dissolution medium, the rotary drive was switched on, and the dissolution kinetics was measured by determining the concentration of the dissolved compound at certain time intervals. The rate of basket rotation was 100 rpm, and the solution samples (2.5 ml) were taken every 10 min over a 60-min period (with replenishing the volume of the dissolution medium by adding the same amount of pure solvent). The drug concentration in the samples was determined by UV spectrophotometry. The drug dissolution process was described in terms of the first-order kinetic equation, and the K sol values were determined by least squares [2].(b) Determining the diffusion rate constants (K d ) of drugs. The diffusion constants were determined using a membrane model simulator of the Sartorius 16750SM type (Germany). The membrane separating the donor and acceptor chambers was made of poly(vinyl acetate) and impregnated with lipids (fatty alcohols and fatty acids). Depending on the combination of impregnating lipid components, it was possible to simulate membranes of the stomach and intestinal walls [2].(c) Determining the lipophilicity constants (log K w ) of drugs. The characteristics of lipophilicity were determined by reverse-phase HPLC on a 4.6´250 mm column with 583 0091-150X/04/3811-0583

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Section: Experimental Chemical Partmentioning

confidence: 99%

Section: Experimental Chemical Partmentioning

confidence: 99%

“…Each experimental point was determined by averaging data obtained for 6 -8 animals. The concentrations of drugs and their metabolites were determined by HPLC as described in [4].…”

Section: Experimental Biological Partmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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