Pharmacokinetic interactions gastrointestinal absorption

In its original formulation as a hard gel capsule (saquinavir-H Invirase), oral saquinavir was poorly bioavailable (about 4% in the fed state). It was therefore largely replaced in clinical use by a soft gel capsule formulation (saquinavir-S Fortovase), in which absorption was increased approximately threefold. However, reformulation of saquinavir-H for once-daily dosing in combination with low-dose ritonavir (see Ritonavir) has both improved antiviral efficacy and decreased the gastrointestinal side effects typically associated with saquinavir-S. Moreover, coadministration of saquinavir-H with ritonavir results in blood levels of saquinavir similar to those associated with saquinavir-S, thus capitalizing on the pharmacokinetic interaction of the two agents. 

M, Muirhead, F, Bochnet and A. Somogyi, Pharmacokinetic drug interactions between triamterene and ranitidine in humans Alterations in renal and hepatic clearances and gastrointestinal absorption, /. Pharmacd. Exp. Ther., 244 734-739 (1988). 

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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