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First-pass metabolism may occur in the liver (for propranolol, lidocaine, clomethiazole, and nitroglycerin) or in the gut (for benzylpenicillin and insulin). [4] The four primary systems that affect the first pass effect of a drug are the enzymes of the gastrointestinal lumen, [5] gastrointestinal wall enzymes, [6] [7] [8] bacterial enzymes [5] and hepatic enzymes.
In particular, the oral route is subject to a high first-pass effect, which results in high levels of testosterone in the liver and consequent hepatic androgenic effects, as well as low potency due to first-pass metabolism in the intestines and liver into metabolites like dihydrotestosterone and androgen conjugates. [2]
Conversely, if it is absorbed by the upper portion of the rectum, progesterone is subject to hepatic first-pass metabolism due to entry into the hepatic portal system via the superior rectal vein. [18] As such, although rectal administration is a parenteral route, it may still be subject to some first-pass metabolism similarly to oral ...
Testosterone is the primary male sex hormone and androgen in males. [3] In humans, testosterone plays a key role in the development of male reproductive tissues such as testicles and prostate, as well as promoting secondary sexual characteristics such as increased muscle and bone mass, and the growth of body hair.
Transdermal estradiol bypasses the intestines and liver and hence the first-pass metabolism that is associated with oral administration. [ 10 ] [ 96 ] In addition, unlike oral estradiol, transdermal estradiol is not associated with supraphysiological concentrations of estrone or estrogen conjugates like estradiol sulfate, and transdermal ...
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[2] [3] However, when a medication is administered via routes other than intravenous, its bioavailability is lower due to intestinal epithelium absorption and first-pass metabolism. Thereby, mathematically, bioavailability equals the ratio of comparing the area under the plasma drug concentration curve versus time (AUC) for the extravascular ...
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