Experimental Pharmacokinetics of Tetramezine in Rats

Abstract

The pharmacokinetics of the new psychotropic agent tetramezine in rats has been studied with the aid of gas chromatography. The drug concentration profiles in the blood, excreta, and urine have been determined. Upon peroral administration, tetramezine is rapidly absorbed from the gastrointenstinal tract, and the maximum drug concentration in the blood plasma is observed within 5 min. The pharmacokinetics of tetramezine upon intravascular and intramuscular injections are dose-dependent and linear within the dose range studied. The average half-elimination times are 0.42 h (i.v.); 0.32 h (i.m.); and 0.42 h (p.o.). The obtained data are important for the subsequent investigation of the drug bioaccessibility and metabolism and for establishing relationships between the drug behavior in vitro, in experiments on animals, and in clinics. 3450091-150X/05/3907-0345

Investigation of tetramezine excretion from rats

“…This coincidence of the drug elimination constants allows some pharmacokinetic parameters to be determined without recourse to invasive sampling techniques. For example, the half-elimination time evaluated as t 1/2 = 0.693/k el = 0.693/1.865 = 0.37 h well agrees with the value t 1/2 = 0.32 h determined from the drug concentration dynamics in the blood plasma upon administration by the same method [4].…”

“…As can be seen, the average rate constant b = 1.87 h -1 deter-mined from data on the urinary excretion does not significantly differ from the value (2.14 h -1 ) obtained from data on the kinetics of drug concentration in the blood plasma upon single intramuscular injection in the same dose (200 mg/kg) [4]. This coincidence of the drug elimination constants allows some pharmacokinetic parameters to be determined without recourse to invasive sampling techniques.…”

“…Since the degree of tetramezine bioavailability upon intramuscular injection is about 64% [4], the amount of drug entering into the blood flow of each rat is on the average about 25.60 mg. Thus, only about 5.2% of the introduced drug is recovered in the unchanged form with urine.…”

Synthesis of monocyclic diaziridines and their fused derivatives

“…9,11 Secondly, diaziridine derivatives are of interest as neurotropically active compounds. [12][13][14][15] Furthermore, diaziridines are prone to ring expansion reactions with electrophilic reagents (ketenes, isocyanates, isothiocyanates, and acylating reagents), which led to the development of new simple methods for the preparation of both known and previously unknown heterocyclic systems. 8,[16][17][18][19][20] And, finally, diaziridines have a high formation enthalpy as a result of the input both of the hydrazine fragment and three-member strained cycle and of low toxicity, which can be potentially useful for replacing hydrazine derivatives in rocket propellants.…”

Experimental evaluation of bioavailability of tetramezine from tablets

“…Previously, we have developed a convenient chromatographic method for the quantitative determination of tetramezine in biological fluids and studied the experimental pharmacokinetics of this drug in rats [2,3]. In the present study, we have studied the bioavailability of tetramezine from ready-to-use tablets and from a solution and compared the drug pharmacokinetics in dogs and rats.…”