Bioavailability INDEX

From an analysis of the key properties of compounds in the World Dmg Index the now well accepted Rule-of-5 has been derived [25, 26]. It was concluded that compounds are most Hkely to have poor absorption when MW>500, calculated octanol-water partition coefficient Clog P>5, number of H-bond donors >5 and number of H-bond acceptors >10. Computation of these properties is now available as a simple but efficient ADME screen in commercial software. The Rule-of-5 should be seen as a qualitative absorption/permeabiHty predictor [43], rather than a quantitative predictor [140]. The Rule-of-5 is not predictive for bioavail-abihty as sometimes mistakenly is assumed. An important factor for bioavailabihty in addition to absorption is liver first-pass effect (metaboHsm). The property distribution in drug-related chemical databases has been studied as another approach to understand drug-likeness [141, 142]. 

Waiver of in vivo bioavailability and bioequivalence studies for immediate release solid oral dosage forms based on a biopharmaceutics classification system. Center for Drug Evaluation and Research, Food and Drug Administration, issued 8/2000, posted 8/31/2000. http //www.fda.gov/cder/guidance/ index, htm... 

Dysregulation of the vascular endothelium has emerged as a critical component of most thrombotic disorders [10, 21]. Often without any anatomical sign of atherosclerosis, many cardiovascular diseases express a vasomotor abnormality termed endothelial dysfunction, indexed clinically as impaired endothelium-dependent vasodilation [31]. Although its mechanism is multifactorial, endothelial dysfunction is characterized by diminished vascular NO production and/or bioavailability [32]. The... 

If this model is selected, one must then decide what variables to use for the ordinate and the abscissa. The parameters must be dose-sensitive, free of confounding variables, easily determined and preferably linear. We have evaluated this approach for estimating the bioavailability of calcium in mechanically deboned meat products (11). Typically, correlations between various bone parameters and dietary calcium are very high (r = 0.943 to 0.999). This is consistent with what others have found for similar parameters (46,47). These correlations are also similar to the those (r = 0.947 to 0.982) between the amount of calcium consumed and calcium retained (11) a good index procedure. 

FDA (August 2000) Guidance for industry Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System, http //www.fda.gov/cder/ guidance/index.htm Biopharmaceutics... 

Theophylline is a narrow therapeutic index drug with significant difference in bioavailability following oral administration. The half-life of the drug is increased by heart failure, cirrhosis and viral infections, in elderly patients, and by certain drugs, such as cimetidine, ciprofloxacin, oral contraceptives and fluvoxamine. The half-life is decreased in smokers, chronic alcoholism, and by certain drugs, such as phenytoin, rifampicin and carbamazepine. 

Highly variable (often associated with poor) bioavailability with low therapeutic index... 

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