Study of influence of additives of tyloxapol on the chromatographic characteristics of the model compounds: the comparative characterization of micellar mobile phases of tyloxapol and Triton X-100.

The chromatographic behavior of model compounds of biomedical significance (organic acids, amino acids, drugs) was investigated using mobile phases modified with tyloxapol. The influence of factors such as concentration of tyloxapol, content of organic modifier and pH of mobile phase on the retention factor of solutes was studied. The results were compared with the data obtained by elution with mobile phases containing Triton X-100 additives, since units of Triton X-100 are repeated in the structure of tyloxapol. Divergence in chromatographic behavior of model compounds was explained by the difference in physico-chemical characteristics (microviscosity, polarity, critical micelle concentration, shape of micelles, etc.) of tyloxapol and Triton X-100 micelles.

Imitation of artificial membrane system via mobile phases with Tween-80 and cholic acid in biopartitioning micellar chromatography.

The chromatographic behaviour of compounds of biomedical significance was studied using micellar mobile phases modified with polyoxyethylene (20) sorbitan monooleate (Tween-80). The influence of the surfactant within the 0.75-4% concentration range on the retention factor of model compounds was investigated. The biological surfactant cholic acid was introduced into the mobile phases in order to approach to the structure of natural membranes, viz. erythrocyte and cytoplasmatic membranes. It was found that curves of dependence of retention factor vs concentration of Tween-80 in the absence and presence of cholic acid in the mobile phase considerably diverge with one another, especially in the 2-3% concentration range of Tween-80 using C18-type support. Increasing the concentration of Tween-80 resulted in the increase of retention factors using phenyl-coated stationary phase.

Interaction of surface-active drugs in rabbits.

The interaction of chlorpromazine and promethazine in vivo has been investigated. The drugs were administered to the rabbit orally as a single dose (100 mg of each drug) as well as simultaneously with an interval of 15 min. The presence of multiple peaks at the separate administration of promethazine and chlorpromazine on the one hand, and increase of number of peaks, symbathic character of kinetic curves of mentioned drugs and its prolonged appearance in the systemic circulation of the blood by simultaneous administration on the other hand, may be explained by the intensive presystem metabolism and surface-activity ability of these drugs, and by the periodic 'lassitude' of liver for their capture and elimination (either presystem or systemic). The micelle formation from these drugs in the gastro-intestinal tract and formation of the mixed micelles on simultaneous administration were also taken into consideration. Chlorpromazine is more strongly captured by the liver at its first pass through it than promethazine, from comparison of pharmacokinetics of these drugs administered separately. Therefore, chlorpromazine on simultaneous administration occupies the sites of the liver which were covered by promethazine at single dose, thereby substituting promethazine and promoting its transferral into the systemic blood circulation. This results in a large increase in promethazine content in blood, additional peaks appear and the presence of promethazine in the blood is prolonged. The influence of chlorpromazine on the kinetics of promethazine is especially obvious when chlorpromazine enters the organism first and more easily occupies those sites in the liver which participate in the capture and elimination of both drugs. Concerning influence of promethazine on the kinetics of chlorpromazine, promethazine reinforces in some way the ability of liver to capture chlorpromazine, thereby intensifying the presystem metabolism of chlorpromazine and inhibiting its own metabolism. The analogous effect was observed in the study of the influence of promethazine on the kinetics of carbamazepine.

Influence of nonionic surfactants on the chromatographic behaviour of proteins in hydrophobic interaction chromatography.

The chromatographic characteristics of proteins in the presence of additives of nonionic surfactants Brij-35 and Tween-80 in the conditions of descending gradient of ammonium sulfate and phenyl-coated polymeric stationary phase were investigated. It was revealed that retention factors of proteins may be regulated by use of mentioned additives. The improvement of resolution is achieved for some hardly separated pairs of proteins, viz. albumin egg/albumin bovine, aldolase/tripsin. A reversion of the elution order is observed for tripsin/chymotrypsinogen A.

Interaction of carbamazepine and promethazine in rabbits.

The interaction of carbamazepine and promethazine in rabbits has been investigated. The influence of this interaction on the processes of biotransformation in the liver was revealed. The drugs were administered as single oral doses (100 mg of each drug) as well as simultaneously with an interval of 15 min. The sequence of administration of the drugs was varied. The influence of promethazine on the pharmacokinetics of carbamazepine is expressed by: (a) strong suppression of carbamazepine's level in plasma and appearance of multiple peaks of carbamazepine; (b) suppression of biotransformation of carbamazepine into carbamazepine-10,11-epoxide at the initial stages and its increase in the intermediate stages. These data are explained by the active capture of carbamazepine by liver at its primary transferal through the liver and sufficient presystem elimination of carbamazepine in the presence of promethazine. The character of kinetic curves of promethazine varies substantially under the influence of carbamazepine. However, this change is not as strong as in case of carbamazepine. The concentration of promethazine in plasma varies slightly and multiple peaks are not observed. The rate of terminal elimination of promethazine varies and abrupt prolonged segments of elimination appear at the initial and terminal stages of the process in return. These data perhaps indicate the induction of biotransformation of promethazine in the presence of carbamazepine-an inductor of microsomal liver enzymes. The changes of kinetics of promethazine and carbamazepine by simultaneous administration as compared with their administration separately, as well as a comparative consideration of pharmacokinetics of promethazine and carbamazepine by simultaneous administration show the existence of competition in the elimination between these drugs and the periodic saturation of liver for their biotransformation.