Interaction of surface‐active drugs in rabbits

Abstract

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.

Studies on the interaction between promethazine and human serum albumin in the presence of flavonoids by spectroscopic and molecular modeling techniques

“…For example, patients taking PMT with ketorolac can cause delirium [15]. The character of kinetic curves of promethazine changed substantially and the elimination of PMT in the blood was prolonged under the influence of carbamazepine and chlorpromazine [16,17]. In addition, patients should be warned not consume anything (drugs and foods) containing caffeine at the treatment by PMT, as caffeine will cause increasing of maximum and current concentration of PMT and its prolongation in organism [18], which indicates that the food-drug interaction should be considered in the period of the drugs treatment.…”

Avoiding Hemolytic Anemia by Understanding the Effect of the Molecular Architecture of Gemini Surfactants on Hemolysis

“…Red blood cells are the most important component of bloodstream that primarily carry oxygen and collect carbon dioxide through hemoglobin with a lifespan of ∼120 days. Many important drugs are aqueous insoluble or sparingly soluble because of their predominantly hydrophobic nature, and hence, they need to be either surface-active or in combination with surface-active molecules to increase their absorption. − However, when surface-active drugs − interact with the blood cell membrane, they can cause hemolytic anemia, which is a quite common side effect of many important drugs. − It is possible to maintain the surface-activity of a drug while reducing the hemolytic anemia by structurally altering some functional groups that possess a greater affinity to interact with the blood cell membrane. , In this study, we try to address this issue by using a variety of surfactant molecules with different molecular architectures that can be used as surface-active agents in biological systems without inducing hemolysis of blood cells.…”