Receptor-Based Dosing Optimization of Erythropoietin in Juvenile Sheep after Phlebotomy

ABSTRACT: The primary objective of this work was to determine the optimal time for administration of an erythropoietin (Epo) dose to maximize the erythropoietic effect using a simulation study based on a young sheep pharmacodynamic model. The dosing optimization was accomplished by extending a Hb production pharmacodynamic model, which evaluates the complex dynamic changes in the Epo recepto

Mathematical modeling in dissolution kinetics and applications of a new nonlinear regression program.

Historically pharmacy has been primarily concerned with the forms in which drugs are administered. Most effort has been directed to making formulations of drugs physically and chemically stable and acceptable to the patient with regard to appearance, colour, taste and smell and form of administration. It has become apparent, however, that other factors are important in drug formulation as techniques in pharmacology, medicine and analysis of drugs in the body improved. Emphasis has been directed toward studying the interactions between drug formulations and the organism and this resulted in the establishment of biopharmaceutics as a distinct field within the pharmaceutical sciences. One of the major biopharmaceutical problems has been absorption in relation to drug formulation. Many very potent drugs have high lipid/ water partition coefficients which facilitates their penetration through biological membranes. While this property lowers the biological barrier and favours absorption, it also paradoxically creates formulation problems because such drugs are frequently only very slightly soluble in water. It is generally accepted that limited absorption after oral intake is frequently the result of slow dissolution. This kind of absorption problem occurs so frequently that bioavailability testing has become an important part of modern drug and dosage form design and production control. Many examples of differences in bioavailability resulting from differences in dissolution behaviour have been given in the literature (1, 2). Research into dissolution kinetics of drugs is therefore of great importance