Binding of Antibiotics to a Soluble Protein from Rat Liver

Performance of a diffusional clearance model for beta-lactam antimicrobial agents as influenced by extravascular protein binding and interstitial fluid kinetics

“…In these cases, the most probable cause for deviations from model behavior is invalidation of assumptions ii and iii: either the agent penetrates into cells or it binds to extravascular components other than albumin. Many antimicrobial agents that are cleared by the liver or kidney must enter cells in these organs and may be bound to ligandin (24) before elimination. However, the mass of drug located in these organs at any time is relatively small and should not affect the gross distributional kinetics of the compound.…”

Protein Binding of Drugs

“…Thus, a more rapid reduction in antimicrobial activity due to the increased availability of the free fraction for elimination via the kidneys would occur. However, the results have shown a small increase in cefapirin concentrations in the presence of acenocoumarin and thus reduced cefapirin elimination, probably because of binding to the intracellular solvent protein ligandin, which binds to a number of anionic drugs (Kornguth et al, 1974).…”

Importance of the Mode of Intravenous Administration on Cephotaxime Concentration in Bile

“…Great differences in biliary excretion are observed even within groups of antibiotics, including the P-lactamines. This group encompasses anti biotics that are secreted into bile in small quantities and others, such as cephoperazone, for which the bile is the main route of elimination [7][8][9][10], These differences of behaviour have been attributed to several causes: (1) different affinity for liver in tracellular proteins such as GSH cationic transferase (ligandin) [11][12][13][14] or anionic substances; (2) molecular weight, when the drug is over the threshold value of 450 [15]; (3) different levels of saturation of the bil iary. The hepatic cell seems to be strongly influenced by its bond with the intracellu lar proteins.…”