Gastrointestinal tract pharmacokinetic interactions

Pharmacokinetics. Warfarin is readily absorbed from the gastrointestinal tract and like all the oral anticoagulants, is more than 90% bound to plasma proteins. Its action is terminated by metabolism in the liver. Warfarin (t/ 36 h) is a racemic mixture of approximately equal amounts of two isomers S (t)/ 35 h) and R 50 h) warfarin, i.e. it is in effect two drugs. S warfarin is four times more potent than R warfarin. Drugs which interact with warfarin affect these isomers differently. 

Ciclosporin is absorbed to a variable extent from the gastrointestinal tract and almost completely metabolized in both the liver and small intestine by CYP3A, which metabolizes a large number of drugs. Inducers, inhibitors, or substrates of CYP3A therefore have the potential to interact with ciclosporin. In addition, ciclosporin has wide pharmacokinetic variability and a narrow therapeutic index. Conversely, ciclosporin can inhibit the hepatic metabolism of other drugs that share the same CYP3A metabolic pathway. 

The particular complexities of antibody pharmacokinetics and their relationship to pharmacodynamics have been thoroughly reviewed by Lobo and coworkers [16]. Many of the characteristics discussed above for macromolecules in general also apply in the case of antibodies. Thus, absorption following subcutaneous or intramuscular administration may be slow, with involvement of lymphatic transport, and attainment of peak blood concentrations may take days. Although absorption of antibodies from the gastrointestinal tract following oral administration to adult humans is very limited, absorption of IgG from the gastrointestinal tract of neonates of several species has been demonstrated [34]. This absorption occurs via interaction with the neonatal receptor for... 

A study in animals found that pretreatment with oral ciclosporin had no effect on the pharmacokinetics of alcohol or acetaldehyde. This suggests that any difference in the alcohol consumption of patients taking ciclosporin is unlikely to have a pharmacokinetic basis. The mechanism by which red wine exerts its effect is not known. White wine does not appear to affect ciclosporin pharmacokinetics," so the interaction is not believed to be an effect of alcohol. Antioxidants in red wine such as resveratrol may inactivate the cytochrome P450 isoenzyme CYP3A4 and this would also be expected to increase ciclosporin levels. The solubility of ciclosporin is decreased in red wine and it is possible that substances in red wine bind ciclosporin in the gastrointestinal tract and reduce its bioavailability. Another study by the same authors suggested that ciclosporin absorption is possibly impaired by P-glycoprotein induction. ... 

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