It contains a number of compounds that can destroy one of the main enzymes, cytochrome P450 3A4
(2004) The structure of human microsomal cytochrome P450 3A4
determined by X-ray crystallography to 2.05-??
This case reiterates the importance of knowledge of drug interactions in day to day practice and the need to be cautious of potential myopathy when prescribing statins to hypothyroid patients, especially in combination with cytochrome P450 3A4
It is lipophilic and insoluble in water and is a substrate for the drug efflux pump p-glycoprotein and the metabolising enzymes cytochrome P450 3A4
and cytochrome P450 3A5 [3,4].
Sildenafil and vardenafil both are metabolised primarily in the liver via the cytochrome P450 (CYP) pathway, mostly by CYP 3A4 and to a lesser extent by CYP 2C9, while tadalafil is metabolised almost solely by the cytochrome P450 3A4
Camptothecin attenuates cytochrome P450 3A4
induction by blocking the activation of human pregnane X receptor.
Most interactions with grapefruit products are thought to result from the inhibition of intestinal cytochrome P450 3A4
Zhou, "Drugs behave as substrates, inhibitors and inducers of human cytochrome P450 3A4
," Current Drug Metabolism, vol.
Differential inhibition of cytochrome P450 3A4
, 3A5 and 3A7 by five human immunodeficiency virus (HIV) protease inhibitors in vitro.
The 5'-hydroxymethyl metabolite of flucloxacillin, generated by cytochrome p450 3A4
, has also been shown in vitro to be directly toxic to biliary epithelium.
"One possible explanation for this difference is that there is a 37% higher clearance rate of amiodarone in females than in males because of differences in cytochrome P450 3A4
activity and the percentage of body fat," the authors reported (Cancer 2013 April 8 2013 [doi.wiley.com/ 10.1002/cncr.27881]).
There are several factors common to drugs that interact with grapefruit: they are all taken by mouth, the have low to intermediate bioavailability 6 meaning only a fraction of the drug will circulate in the bloodstream, with the rest digested 6 and all of them are broken down by an enzyme called cytochrome P450 3A4
, also known as CYP3A4.