Binding of Cetain Antispsmodic Drugs toHuman plasma proteins and their supstitutes

Drug binding to various serum and tissue proteins can affect the therapeutic, pharmacodynamic and toxicologic actions of these drugs. Protein binding may also exert a profound effect on the drug distribution. The protein-drug complex may act as a transport system to carry the drug to the sites of action; this is extremely important for drugs that exhibit low solubility in water. Protein binding slows the disappearance of free drug from the plasma into tissues by decreasing the concentration gradient. It also provides a source of free drug to replace that removed by various distribution and elimination processes. The binding equilibrium is often described by an association constant. Such information is useful in establishing a proper dosage regimen. The binding to human serum albumin of a new drug should be examined, especially if the drug is an acidic molecule. The human serum albumin can bind both acidic and basic drugs. Disease status was reported to affect the binding of drugs to human serum albumin. Mebeverine hydrochloride and drotaverine hydrochloride are twoy,tspasmodiC drugs widely used in Egypt. The work in this thesis deals with the binding of these drugs to human serum albumin and to dextran, one of plasma substitutes. The factors that can affect the nding process was investigated. The release of these s from drug-protein complex was also studied. Finally e plasma protein binding of these drugs in healthy and nal diseased volunteers was demonstrated. Le this thesis is divided into three parts: I: Binding of mebeverine hydrochloride to plasma proteins and their substitutes. Part II: Binding of drotaverine hydrochloride to plasma proteins and their substitutes. Part III: Binding of mebeverine hydrochloride and drotaverine hydrochloride to human plasma proteins of healthy and renal diseased volunteers.