FACTORS AFFECTING PHARMACOKINETIC DISPOSITION OF DRUGS
Journal Title: International Research Journal of Pharmacy (IRJP) - Year 2011, Vol 2, Issue 5
Abstract
Absorption of drugs from the gastrointestinal tract is a complex process the variability of which is influenced by many physicochemical and physiologic factors. The two most important physicochemical factors that affect both the extent and the rate of absorption are lipophilicity and solubility. The rate and extent of absorption are governed by the solubility, permeability and stability of the drug, with solubility being a pH-dependent parameter for weak acids and bases. The gastrointestinal tract can be viewed as discrete sections with a variety of differential local pH environments ranging from the acidic stomach to the more basic small intestine. The multiple peaking, double peaking or secondary peaking phenomena can occur in the disposition of a variety of xenobiotics during drug development (the pre-clinical phase) and in subsequent clinical studies and use. The physicochemical and physiological mechanisms underlying the occurrence of this phenomenon are often multi factorial and include but are not limited to solubility-limited absorption, modified-release formulations, complexation, enterohepatic recirculation, gastric emptying and the intestinal transit time, site-specific absorption, gastric secretion-enteral reabsorption. Double peak absorption has been described with several orally administered drugs such as cimetidine furosemide, piroxicam, ranitidine, talinolol, alprazolam and phenazopyridine.
Authors and Affiliations
Hiren Mehta , Paresh Patel , Varsha Galani
Keywords
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