Intestinal metabolism promotes regional differences in apical uptake of indinavir: coupled effect of P-glycoprotein and cytochrome P450 3A on indinavir membrane permeability in rat.

The purpose of this study was to investigate transport and metabolism contributions to low indinavir permeability in rat ileum and enhanced drug permeability in the jejunum. Permeability models utilized included single pass in situ rat intestinal perfusion and rat intestinal tissue mounted in Ussing chambers. Intestinal metabolism was measured by fractional appearance of metabolite (F(met)), determined as the percentage of the predominant metabolite M6 over luminal loss of indinavir in the perfusion model.

Medicinal chemistry in the development of societies. Biodiversity and natural products.

This document has been elaborated by the IUPAC Medicinal Chemistry section and is backed by a large number of scientists, many of whom have had direct involvement and whose names appear at the end of the article. This work discusses the role that the discovery of new medicinal agents has in the development of societies as well as in the conservation of biodiversity in terms of work carried out on natural products. Also included are several recommendations for countries which are presently in search of their own scientific and technological development in medicinal agents.

QSAR model for drug human oral bioavailability.

The quantitative structure-bioavailability relationship of 232 structurally diverse drugs was studied to evaluate the feasibility of constructing a predictive model for the human oral bioavailability of prospective new medicinal agents. The oral bioavailability determined in human adults was assigned one of four ratings and analyzed in relation to physicochemical and structural factors by the ORMUCS (ordered multicategorical classification method using the simplex technique) method. A systematic examination of various physicochemical parameters relating primarily to absorption, and structural elements which could influence metabolism, was carried out to analyze their effects on the bioavailabilty classification of drugs in the data set.

University education of medicinal chemists: comparison of eight countries.

Medicinal chemists are mainly taught in faculties or schools of pharmacy and are available for employment. Yet major pharmaceutical research companies seek organic chemists, rather than medicinal chemists, for new drug discovery. This apparent contradiction led the Medicinal Chemistry Section of IUPAC to send a questionnaire regarding postgraduate academic education for medicinal chemists to the faculties or schools of pharmacy in eight countries, namely, France, Germany, Italy, Japan, Spain, Switzerland, UK and USA.

The measurement of molecular diversity by receptor site interaction simulation.

The assembly of large compound libraries for the purpose of screening against various receptor targets to identify chemical leads for drug discovery programs has created a need for methods to measure the molecular diversity of such libraries. The method described here, for which we propose the acronym RESIS (for Receptor Site Interaction Simulation), relates directly to this use. A database is built of three-dimensional representations of the compounds in the library and a set of three-point three-dimensional theoretical receptor sites is generated based on putative hydrophobic and polar interactions.