salicylates and 3-hexylsalicylic-acid

The influence of lipophilic counter ions on the transport of the hydrophilic drugs pholedrine and bretylium across artificial lipid membranes has been studied using a permeation model system. The transport of both drugs was markedly enhanced by hexylsalicylate and by salts of fatty acids with a maximum at decanoate. The transport of pholedrine was additionally increased by bile salts such as desoxycholate.

Topics: Bretylium Compounds; Fatty Acids; Lipids; Membranes, Artificial; Methamphetamine; Permeability; Pharmaceutical Preparations; Salicylates; Spectrophotometry, Ultraviolet

The simultaneous i.v. administration of equimolar doses of bretylium and hexylsalicylic acid results in an increase in plasma area under the curve value of both substances in comparison with their separate administration. The higher plasma levels of both compounds were associated with a reduced renal excretion and an increased biliary elimination. However, the increase in biliary excretion did not compensate for the reduced elimination of bretylium and hexylsalicylic acid via the kidney. The results presented in this paper give further evidence that ion-pairing in-vivo may result in altered pharmacokinetics of drugs particularly due to changes in biliary or renal excretion.

Topics: Animals; Bile; Biological Transport; Bretylium Compounds; Drug Combinations; Female; Injections, Intravenous; Ions; Kidney; Male; Rabbits; Salicylates

Topics: Animals; Bretylium Compounds; Dogs; Ion Exchange; Male; Salicylates

Following i.v. administration of the hydrophilic drug bretylium (1) and the lipophilic hexylsalicylic acid (2) in rats the plasma levels of 2 were increased due to an increased intestinal reabsorption of 2. Under these conditions the biliary eliminated amount of 2 was 8 times higher than that following the administration of 2 alone. The eneteroheptic circulation of 2 was found to be interrupted following i.v. administration of 1 and 2 and additional oral administration of an anionic exchanger. Then the plasma levels of 2 were not influenced by 1. On other hand the plasma levels of 2 appear to be too low in order to influence those of 1.

Topics: Animals; Bile; Bretylium Compounds; Injections, Intravenous; Male; Rats; Rats, Inbred Strains; Salicylates

Based on previous in vitro studies it could be shown that ion-pair-formation with the lipophilic hexylsalicylic acid (1) influences the pharmacokinetics of the hydrophilic drug pholedrine (2) which is ionized in all physiological media. After oral combination with 1 an increase of the AUC of 2 could be observed. This finding is due both to the increase of the absorption of 2 and to the decrease of the elimination of 2. After i.v. application the high biotransformation rate of 2 prevents an influence of 1.

Topics: Administration, Oral; Animals; Injections, Intravenous; Methamphetamine; Rabbits; Salicylates; Sympathomimetics

Based on in vitro results it was found that the pharmacokinetic parameters of the hydrophilic drug bretylium (2) can be influenced by an ion-pair-formation with the lipophilic hexylsalicyclic acid (1). After simultaneous i.v. application of 1 and 2 on rabbits a significant increase of the AUC of 2 was observed. Under these conditions a marked increase of the AUC and the MRT of 1 was also obtained, since the blood levels of 2 are high enough for such an influence. A combined rectal application of 1 and 2 causes an increase of the AUC of 2.

Topics: Administration, Oral; Animals; Bretylium Compounds; Drug Interactions; Injections, Intravenous; Rabbits; Salicylates