Evaluation of drug-drug interaction (DDI) involving circulating inhibitory metabolites of perpetrator drugs has recently drawn more attention from regulatory agencies and pharmaceutical companies. Here, using amiodarone (AMIO) as an example, we demonstrate the use of physiologically based pharmacokinetic (PBPK) modeling to assess how a potential inhibitory metabolite can contribute to clinicall...

Rat skeletal-muscle hexokinase was partially purified by ammonium sulphate fractionation and gel filtration. The mechanism of the skeletal-muscle hexokinase was studied kinetically by initial-velocity analysis and product inhibition. Glucose 6-phosphate was a non-competitive inhibitor of glucose and ATP. ADP was a non-competitive inhibitor of glucose and a competitive inhibitor of ATP. The data...

The catalytic oxidation of catechol by crude preparations of mushroom tyrosinase was studied by a method yielding data on initial reaction velocities. Graphical analysis of the results suggests that an excess of catechol inhibits its own oxidation by a competitive process, thus accounting for the observed optimum in the substrate concentration. However, added phenol, though itself a substrate, ...

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the formation of prostaglandins by cyclo-oxygenases (COX). The discovery of a second COX isoform (COX-2) associated with inflammation led to agents that selectively inhibit COX-2, e.g. celecoxib. We evaluated the kinetics of inhibition of celecoxib and several NSAIDs. Celecoxib displays classic competitive kinetics on COX-1 (Ki=10-16 microM...

Objective(s):Involvement of tyrosinase in the synthesis of melanin and cell signaling pathway has made it an attractive target in the search for therapeutic inhibitors for treatment of different skin hyperpigmentation disorders and melanoma cancers. Materials and Methods: In the present study, we conducted a comprehensive kinetic analysis to understand the mechanisms of inhibition imposed by 2-...

Backward inhibition in a two-layer connectionist network can be used as an alternative to, or an enhancement of, the competitive model for unsupervised learning. Two feature discovery algorithms based on backward inhibition are presented. It is shown that they are superior to the competitive feature discovery algorithm in feature independence and controllable grain. Moreover, the representation...

The purpose of this note is to posit and discuss the concept of "competitive inhibition potential" (CIP), which is an in vivo index of the ability of a competitive inhibitor to elevate plasma concentrations of drug substrates, when the competitive inhibitor is administered at its usual and customary dose.