Utility of in vitro systems and preclinical data for the prediction of human intestinal first-pass metabolism
during drug discovery and preclinical development.
Transdermal delivery can also bypass the first-pass metabolism
and can offer the additional benefit of extended release of the API.
of ethanol: gastric or hepatic, mountain or molehill.
Zhang et al., "Intestinal absorption and first-pass metabolism
of polyphenol compounds in rat and their transport dynamics in caco-2 cells," PLoS ONE, vol.
Therefore the Sprague-Dawley rat liver microsomes may be useful for assessing herb-drug interaction in the hepatic first-pass metabolism
responsible for CYP1A2 at the early drug-discovery stage because of similar typical substrates and metabolism activities as humans.
Other possible factors contributing to observed lower mean 11-OH-THC [C.sub.max] and [AUC.sub.0 [right arrow] 10.5 h] after high-dose Sativex were facilitated THC absorption through the oral mucosa and reduced first-pass metabolism
. In the present study, THC bioavailability was enhanced when THC was administered by oromucosal spray, compared with oral administration, although differences did not reach statistical significance.
Orally disintegrating tablets dissolve on first contact with saliva and undergo pre-gastric absorption, minimizing first-pass metabolism
and yielding high plasma levels.
Moreover, when the drug enters the body via this route, it undergoes first-pass metabolism
in the liver.
Unfortunately, a major drawback of Invirase was its limited bioavailability due to incomplete absorption and extensive first-pass metabolism
. The poor bioavailability was such a critical factor that the manufacturer of saquinavir reformulated the preparation.
A significant correlation between gastric ADH activities and first-pass metabolism
of ethanol has been reported, suggesting that activities can be rate limiting under certain conditions.
Lieber notes that studies of males reported by his team in the February 1989 GASTROENTEROLOGY indicate that some drugs -- including cimetidine, widely presribed to control gastric ulcers -- can inhibit the stomach's first-pass metabolism
The data simulation model contained elements of stomach emptying, intestinal and colon transit, first-pass metabolism
in the small intestine and multi-compartment pharmacokinetics.