Co-administered drugs

The expression of a significant gut wall first-pass extraction ratio has several implications for affected drugs. First, oral bioavailability is lower than would be expected from the extent of absorption and the hepatic first-pass extraction. Second, the variability in expression of gut wall metabolic enzymes and transporters can lead to significant variability in gut wall first-pass extraction and thus oral bioavailability. Finally, the site of expression of these enzymes and transporters (i.e., the villus tip) brings them into contact with potentially co-administered drugs or dietary constituents, which could be inhibitors or inducers. Thus, there is the potential for drug-drug interactions at the level of the gut wall. 

These methods have been used since the 1970s they usually require little or no sample preparation and are rapid and easy to use. However, immunoassay has two limitations. First, it does not differentiate between active drugs and similar molecules such as metabolites or co-administered drugs.9,11 Thus, cross-reactivity is a common problem. Second, its use is limited to only those drugs for which antibodies are available. 

Gyno that fails to react to these drugs normally must be removed by surgery. DHT derivatives can cause increases endogenous estrogen production also in some individuals. Cytadren was a commonly co-administered drug with Nolvadex. 

Substantial matrix effects can be specific for individual patients samples, e.g. due to co-administered drugs or other xenobiotics. It is in general tried to detect such samples by assessing the peak areas of the internal standard compound over a whole series Outliers with respect to the peak area of the internal standard may indicate unusually pronounced matrix effects in an individual sample. In such cases it is speculative if the evident matrix effects affect analyte and internal standard to an identical degree, and it is up to the valuation of the analyst if quantitative results of such samples may be reported or not. Re-analysis after dilution can be useful in case of evident matrix effects—given sufficiently high analyte concentration in the respective sample. 

SSRIs inhibit hepatic CYP isozymes and can thereby increase the activity of co-administered drugs that are... 

SSRIs can provoke 5HT neurotoxicity (the 5HT syndrome) through pharmacodynamic interactions with other drugs that also potentiate 5HT function. Often the ability of the interacting drug to facilitate 5HT function is well known, as is the case, for example, when SSRIs are combined with monoamine oxidase inhibitors or lithium. In other cases, however, the potential 5HT activity of the co-administered drug is not widely known. The ability of the antibiotic linezolid to inhibit MAO and thereby to cause 5HT neurotoxicity in combination with SSRIs has been noted previously (SEDA-27, 14), and further cases have now been reported. 

TCAs FLUOROURACIL, IMATINIB, LEFLUNOMIDE Possible t plasma concentrations of these cytotoxics Inhibition of CYP2C9-mediated metabolism. The clinical significance of this depends upon whether alternative pathways of metabolism are also inhibited by co-administered drugs Warn patients to report t side-effects and monitor blood count carefully... 

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