Basic drugs, oral absorption

Bernkop-Schnurch A, Humenberger C, Yalenta C (1998) Basic studies on bioadhesive delivery systems for peptide and protein drugs. Int J Pharm 165(2) 217-225 Chae SY, Jang M-K, Nah J-W (2005) Influence of molecular weight on oral absorption of water soluble chitosans. J Control Rel 102(2) 383-394 Cho EC, Lim HJ, Shim J, Park JY, Dan N, Kim J, Chang I-S (2007) Effect of polymer characteristics on structure of polymer-liposome complexes. J Colloid Interf Sci 311(1) 243-252... 

Formation of soluble hydrochlorides of basic drugs does not necessarily result in improved bioavailability as was illustrated by comparative absorption studies of tetracyclines and lincomycin and their salts. " " Tetracycline-free bases gave higher plasma levels than their hydrochloride salts, while lincomycin hydrochloride had a lower bioavailability than the hexadecylsulfa-mate salts. These differences have been attributed to a common ion effect with gastric HCl following oral administration. 

This chapter provides basic information on the physicochemical mechanisms of drug absorption and how the processes of absorption are affected by the physicochemical properties of the drug and its formulation, by the interaction of the drug with the aqueous phase and by the nature of the membrane. Oral absorption is discussed in some detail and the influence of the following in determining bioavailability should become clear ... 

Changing the pK of an acidic or basic group in a molecule so that more of the compound exists in the ionized form at physiological pH lowers log D (at about pH 7) and, in general, should improve aqueous solubility. The improvement in solubility is limited, however, if the solubility of the neutral form of the compound (the inherent solubility) is very low. The situation is worsened if the starting pK is far from 7. We find this to be a particular problem with weak bases. Weakly basic pyridines, quinolines, quinazo-lines and thiazoles seem to be frequent members of combinatorial libraries. Understanding the ionization behavior of drugs and how this property relates to oral absorption is extremely complex and likely beyond the capability (and interest) of many medicinal chemists. The reader is referred to an excellent recent review in this complex area. ... 

Because of their mechanism of action, bile acid sequestrants can potentially bind with and decrease the oral absorption of almost any other drug. Because these anion-exchange resins contain numerous positive charges, they are much more likely to bind to acidic compounds than to basic compounds or nonelectrolytes. This is not an absolute, however, because cholestyramine and colestipol have been reported to decrease the oral absorption of propranolol (a base) and the lipid-soluble vitamins. A, D, E, and K (nonelectrolytes). As a result, the current recommendation is that all other oral medication should be administered at least 1 hour before or 4 hours after cholestyramine and colestipol. Interestingly, this drug interaction has been used in a beneficial manner to treat digitalis overdose and toxicity. 

Bergstrom CAS (2005) In silico predictions of drug solubility and permeability two rate-limiting barriers to oral drug absorption. Basic Clin Pharmacol Toxicol 96 156-161. 

Excretion of drugs will be affected by the pH of the urine. If the urine is acidic, weak bases are ionized and there will be poor re-absorption. With basic urine, weak bases are non-ionized and there is more re-absorption. The pH of the urine can be artificially changed in the range 5-8.5 oral administration of sodium bicarbonate (NaHCOs) increases pH values, whereas ammonium chloride (NH4CI) lowers them. Thus, urinary acidification will accelerate the excretion of weak bases and retard the excretion of weak acids. Making the urine alkaline will facilitate the excretion of weak acids and retard that of weak bases. 

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