Transporters intestinal absorption

PatU SD, Ngo LY, Glue P, Unadkat JD (1998) Intestinal absorption of ribavirin is preferentially mediated by the Na-l—nucleoside purine (Nl) transporter. Pharm Res 15 950-952... 

Yu LX, Lipka E, Crison JR and Amidon GL. Transport approaches to the bio-pharmaceutical design of oral drug delivery systems prediction of intestinal absorption. Adv Drug Deliv Rev 1996 19 359-76. 

Hollander, D. and Ruble, P.E., P-Carotene intestinal absorption bile, fatty acid, pH, and flow rate effects on transport, Am. J. Physiol, 235, E686, 1978. 

Clark, D. Rapid calculation of polar molecular surface area and its application to the prediction of transport phenomena. 1. Prediction of intestinal absorption. J. Pharm. Sci. 2000, 88, 807-814. 

For 31 passively transported dmgs, excellent sigmoidal relationships were found between human intestinal absorption and their H-bond acceptor and donor factors [65] ... 

A volume-related term (expressed by polarizability) and electrostatics (expressed by partial atomic charge) made minor contributions to intestinal absorption in humans. Lipophilicity, expressed by logP or logD values, shows no correlation with the human absorphon data. Recently, similar results were obtained for 154 passively transported drugs on the basis of surface thermodynamics descriptors [39] ... 

FIGURE 29-2. Levodopa absorption and metabolism. Levodopa is absorbed in the small intestine and is distributed into the plasma and brain compartments by an active transport mechanism. Levodopa is metabolized by dopa decarboxylase, monoamine oxidase, and catechol-O-methyltransferase. Carbidopa does not cross the blood-brain barrier. Large, neutral amino acids in food compete with levodopa for intestinal absorption (transport across gut endothelium to plasma). They also compete for transport across the brain (plasma compartment to brain compartment). Food and anticholinergics delay gastric emptying resulting in levodopa degradation in the stomach and a decreased amount of levodopa absorbed. If the interaction becomes a problem, administer levodopa 30 minutes before or 60 minutes after meals. 

BH Stewart, AR Kugler, PR Thompson, NN Bock-brader. A saturable transport mechanism in the intestinal absorption of gabapentin is the underlying cause of the lack of proportionality between increasing dose and drug levels in plasma. Pharmaceut Res 10 276-281, 1993. 

Artursson, R, Epithelial transport of drugs in cell culture. I A model for studying the passive diffusion of drugs over intestinal absorptive (Caco-2) cells, J. Pharm. Sci. 79, 476-482 (1990). 

Mammalian intestinal absorption requires the presence of two receptors and two transporters, which is itself a unique feature. Specific transporters such as intrinsic factor, transcobalamin, and haptocorrin have been characterized,1113 as well as a number of receptors for passage across cell membranes. A number of biochemical studies on cell uptake1114 and receptors1115,1116 of cobala-mins have been reported. Genetic disorders that impair the synthesis, transport, or transmembrane passage of cobalamins and their consequences have been reviewed.1117,1118... 

The coupling of solute transport in the GI lumen with solute lumenal metabolism (homogeneous reaction) and membrane metabolism (heterogeneous reaction) has been discussed by Sinko et al. [54] and is more generally treated in Cussler s text [55], At the cellular level, solute metabolism can occur at the mucosal membrane, in the enterocyte cytosol, and in the endoplasmic reticulum (or microsomal compartment). For peptide drugs, the extent of hydrolysis by lumenal and membrane-bound peptidases reduces drug availability for intestinal absorption [56], Preferential hydrolysis (metabolic specificity) has been targeted for reconversion... 

M Asgharnejad. Investigation into intestinal transport and absorption of an amino acid, amino acid analougue and its peptideomimetic prodrug. PhD dissertation, Chapter IV. pp 109-127, The University of Michigan, 1992. 

M Hu. Investigation into drug and drug analogs transported by the peptide carrier system Intestinal absorption of captopril and of peptidyl derivatives of methyldopa. PhD Thesis, College of Pharmacy, University of Michigan, 1988. 

In Section III, emphasis was placed on flux kinetics across the cultured monolayer-filter support system where the passage of hydrophilic molecular species differing in molecular size and charge by the paracellular route was transmonolayer-controlled. In this situation, the mass transport barriers of the ABLs on the donor and receiver sides of the Transwell inserts were inconsequential, as evidenced by the lack of stirring effects on the flux kinetics. In this present section, the objective is to give quantitative insights into the permeability of the ABL as a function of hydrodynamic conditions imposed by stirring. The objective is accomplished with selected corticosteroid permeants which have been useful in rat intestinal absorption studies to demonstrate the interplay of membrane and ABL diffusional kinetics (Ho et al., 1977 Komiya et al., 1980). 

JN Cogburn, MG Donovan, CS Schasteen. A model of human small intestinal absorptive cells. 1. Transport barrier. Pharm Res 9 210-216, 1991. 

The first study was conducted to determine whether carotenoids and cholesterol share common pathways (transporters) for their intestinal absorption (During et al., 2005). Differentiated Caco-2 cells on membranes were incubated (16 h) with a carotenoid (1 pmol/L) with or without ezetimibe (EZ Zetia, an inhibitor of cholesterol transport), and with or without antibodies against the receptors, cluster determinant 36 (CD36) and scavenger receptor class B, type I (SR-BI). Carotenoid transport in Caco-2 cells (cellular uptake + secretion) was decreased by EZ (lOmg/L) as follows P-C and a-C (50% inhibition) P-cryptoxanthin and LYC (20%) LUT ZEA (1 1) (7%). EZ reduced cholesterol transport by 31%, but not retinol transport. P-Carotene transport was also inhibited by anti-SR-BI, but not by anti-CD36. The inhibitory effects of EZ and anti-SR-BI on P-C transport... 

Uptake and transport of the ACE-inhibitor ceronapril (SQ 29852) by monolayers of human intestinal absorptive (Caco-2) cells in vitro, Int. 

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