Small intestine, pharmacokinetic

The advantage of the mixing tank model approach is its relative simplicity, intuitive accessibility, and easy correlation with pharmacokinetic models. However, the physical basis for considering a segment of the small intestine as one or more serial mixing tanks is limited, although such an assumption has been commonly and successfully utilized in the physical and biological sciences. 

After oral ingestion, ethanol pharmacokinetics must take into account (1) Absorption from the gastrointestinal tract. Since ethanol is absorbed most efficiently from the small intestines, the rate of gastric emptying is an important factor that governs the rate of rise of blood alcohol concentration (BAC), i.e., the slope of the ascending limb of the BAC-time curve, and the extent of first pass metabolism of ethanol by the liver and stomach. (2) Distribution of ethanol in the body. Ethanol distributes equally in total body water, which is related to the lean body mass of the person, and (3) the elimination of ethanol from the body, which occurs primarily by metabolism in the liver, first to acetaldehyde and then to acetate [7]. 

Devries MH, Rademaker CM, Geerlings C, Vandijk A and Noordhoek J (1989) Pharmacokinetic Modeling of the Effect of Activated-Charcoal on the Intestinal Secretion of Theophylline, Using the Isolated Vascularly Perfused Rat Small-Intestine. J Pharm Pharmacol 41 pp 528-533. 

K. Hosoya, M. Tomi, M. Takayama, Y. Komokata, D. Nakai, T. Tokui, K. Nishimura, M. Ueda, M. Obinata, S. Hori, S. Ohtsuki, G. L. Amidon, and T. Terasaki. Transporter mRNA expression in a conditionally immortalized rat small intestine epithelial cell line (TR-SIE). Drug Metabol. Pharmacokinet. 19 264-269 (2004). 

Pharmacokinetics Rapidly absorbed from small intestine. Extensive metabolism in kidneys. Primarily excreted in feces minimal excretion in urine. Half-life 5-8 hr. 

Pharmacokinetics Moderately absorbed from the small intestine (absorption depends on presence of vitamin D metabolites and patient s pH). Primarily eliminated in feces. 

Pharmacokinetics Readily absorbed from small intestine. Metabolized in liver. Partially eliminated in urine. Not removed by hemodialysis. Half-life up to 96 hr. 

Pharmacokinetics Well absorbed following oral administration. Protein binding greater than 90%. Metabolized in the small intestine and liver. Excreted by the kidneys and bile. Half-life 22 hr... 

Mecfianism of Action A cinchona alkaloid that relaxes skeletal muscle by increasing the refractory period, decreasing excitability of motor end plates (curare-like), and affecting distribution of calcium with muscle fiber. Antimalaria Depresses oxygen uptake, carbohydrate metabolism, elevates pH in intracellular organelles of parasites. Therapeutic Effect Relaxes skeletal muscle produces parasite death. Pharmacokinetics Rapidly absorbed mainly from upper small intestine. Protein binding 70%-95%. Metabolized in liver. Excreted in feces, saliva, and urine. Half-life 8-14 hr (adults), 6-12 hr (children). 

The pharmacokinetic profile is different with different compounds. Diazepam after oral administration is completely and rapidly absorbed from the proximal small intestine. Oxazepam is least rapidly absorbed while lorazepam is an intermediately absorbed between these two. They are metabolised in liver by dealkylation and hydroxylation and excreted in urine as glu-curonide conjugates. They cross the placental barrier and are secreted in milk. 

Doherty MM, Charman WN. The mucosa of the small intestine how clinically relevant as an organ of drug metabolism Clin Pharmacokinet 2002 41(4) ... 

Barthe L, Woodley JF, Kenworthy S Houin G. 1998. An improved everted gut sac as a simple and accurate technique to measure paracellular transport across the small intestine. Eur J Drug Metab Pharmacokinet 23 313-323. 

Preliminary pharmacokinetic behavior can be tested through a number of whole cell assays. Most commercially successful drugs are administered orally, meaning the drug must be able to enter the bloodstream by crossing membranes in the intestines. The most common membrane permeability assay is performed by monitoring the absorption and secretion of a compound by colon carcinoma cells (Caco-2). Diffusion across Caco-2 cell membranes is considered to be a valid model for molecular transport in the small intestines.16... 

Due to its compartmental nature, the CAT model can be easily coupled with the disposition of drug in the body using classical pharmacokinetic modeling. In this respect the CAT model has been used to interpret the saturable small-intestinal absorption of cefatrizine in humans [175]. 

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