Enhanced oral bioavailability

C. Structural modification by placing the hydroxy groups at positions 3 and 5 of the phenyl ring has resulted in compounds that are not substrates for COMT, resulting in lower rates of metabolism and enhanced oral bioavailability compared to catecholamines. 

Woo, J.S., et al. 2003. Enhanced oral bioavailability of paclitaxel by coadministration of the P-glycoprotein inhibitor KR30031. Pharm Res 20 24. 

D Emanuele, A., Jevprasesphant, R., Penny, J., and Attwood, D. The use of a dendrimer-propranolol prodrug to bypass efflux transporters and enhance oral bioavailability. J. Control. Release 95(3) 447-453, 2004. 

Carreno-Gomez B. and Duncan R. Compositions with enhanced oral bioavailability. US patent, 2002. 

Recent studies have shown that in addition to their mucoadhesive effects, these polymers can also enhance oral bioavailability by inhibiting enzymes which deactivate the dmg moiety in the GI tract. Both... 

Karenitedn (11, Figure 2.2) is a very lipophilic compound that exhibits more potent cytotoxic activity than camptothecin with both in vitro and in vivo scenarios. In addition to superior in vitro potency, its increased lactone stability and enhanced oral bioavailability are potential clinical advantages [108]. Karenitecin showed significant activity in metastatic melanoma and the dose-limiting toxicity consisted of neutropenia and thrombocytopenia [109]. 

These preparations are primarily intended to achieve faster onset of action for drugs such as analgesics, antipyretics, and coronary vasodilators. Other advantages include enhanced oral bioavailability through transmucosal delivery and pregastric absorption,... 

Zydis system A freeze-dried, porous tablet Enhanced oral bioavailability Maxalt-MLT (Rizatriptan benzoate) ... 

While employing this approach for enhancing oral bioavailability of poorly soluble drugs, in which drug absorption is dissolution-rate limited, the following considerations must be taken into account ... 

R.P. Scherersol system Liquid formulations for softgels, which incorporates the drug in a microemulsion preconcentrate or microemulsion form. Oral delivery of proteins and peptides enhanced oral bioavailability with reduced inter- and intraindividual variability in pharmacokinetics of certain drugs. Sandimmune Neoral (cyclosporine). 

CCK-B selectivity is improved over that of L-365,260 (507, 508). The pyridyl group in (125) provides a significant enhancement in oral bioavailability relative to the phenyl analog. Replacement of the 3-methyl group in (125) with basic moieties (NHMe, NMe2) likewise maintains the receptor binding profile and enhances oral bioavailability (509). 

Gao P, Guyton ME, Huang T, Bauer J, Stefanski K, and Lu L. Enhanced Oral Bioavailability of a Poorly Water Soluble Drug PNU-91325 by Supersaturable Formulations. Drug Dev Ind Pharm 200 30 221-229. 

Zou WW, Sun WT, Zhang N, et al. Enhanced oral bioavailability and absorption mechanism study of N3-0-toluyl-fluorouracU-loaded liposomes. J Biomed Nanotechnol 2008 4 90-98. 

Strategies for Enhancing Oral Bioavailability and Brain Penetration... 

Otagiri, M., Imai, T., Uekama, K. Enhanced oral bioavailability of anti-inflammatory drug flurbiprofen in rabbits by tri-O-methyl-p-cyclodextrin complexation. J. Pharmacobio-Dynam. 1982, 5, 1027-1029. 

Active components in grapefruit juice include furanocoumarins capable of inhibiting the metabolism of many drugs, including alprazolam, atorvastatin, cisapride, cyclosporine, and midazolam. Such compounds may also enhance oral bioavailability by inhibiting drug transporters in the Gl tract responsible for intestinal efflux of drugs,... 

Methyl-substituted phosphorothioate oligonucleotides have recently been reported to be more stable than their parent compounds in mice and to display enhanced oral bioavailability (328, 349). The analogs dis-pl ed tissue distribution similar to that of the parent phosphorothioate. Similarly, we have compared the ph8irmacokinetics of 2 -0-pro-... 

In recent years there has been an increased interest in the utility of lipid-based delivery systems to enhance oral bioavailability (4). It is generally known that membrane permeability is directly correlated to a drug s water-lipid partition coefficient however, the systemic availability of highly lipophilic drugs is impeded by their low aqueous solubility. In an effort to improve this solubility-limited bio-availabiliy,formulators have turned to the use of lipid excipients to solubilize the compounds before oral administration. Several formulations are currently on the market, for example, Sandimmun/Neoral (cyclosporin microemulsion), Norvir (ritonavir), and Fortovase (saquinavir)... 

Esomeprazole 26 Gastric proton pump (inhibitor) Analog of omeprazole (S)-Enantiomer of omeprazole, which is racemic Enhanced oral bioavailability Esophagitis GI tract... 

From detailed cell cultural studies these chitosan derivatives were shown to promote chondrogenesis. Chitosan nanoparticles are shown to enhance oral bioavailability and intestinal absorption of peptide and protein formulations. By ionotropic gelation of chitosan with tripolyphophate anions insulin-loaded nanoparticles have been prepared [230]. 

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