Skip to main content

Month: October 2012

Methods of Solving Rapid Binding Target-mediated Drug Disposition Model for Two Drugs Competing for the Same Receptor

By

The target-mediated drug disposition (TMDD) model has been adopted to describe pharmacokinetics for two drugs competing for the same receptor. A rapid binding assumption introduces total receptor and total drug concentrations while free drug concentrations C (A) and C (B) are calculated from the equilibrium (Gaddum) equations. The Gaddum equations are polynomials in C (A) and C (B) of second degree that have explicit solutions involving complex numbers. The aim of this study was to develop … Continued

Physiologically-based Modeling of Pravastatin Transporter-mediated Hepatobiliary Disposition and Drug-drug Interactions

By

To develop physiologically based pharmacokinetic (PBPK) model to predict the pharmacokinetics and drug-drug interactions (DDI) of pravastatin, using the in vitro transport parameters. In vitro hepatic sinusoidal active uptake, passive diffusion and canalicular efflux intrinsic clearance values were determined using sandwich-culture human hepatocytes (SCHH) model. PBPK modeling and simulations were implemented in Simcyp® (Sheffield, UK). … Continued

In Vivo-formed Versus Preformed Metabolite Kinetics of Trans-resveratrol-3-sulfate and Trans-resveratrol-3-glucuronide

By

Metabolites in safety testing have gained a lot of attention recently. Regulatory agencies have suggested that the kinetics of preformed and in vivo-formed metabolites are comparable. This subject has been a topic of debate. We have compared the kinetics of in vivo-formed with preformed metabolites. trans-3,5,4′-Trihydroxystilbene [trans-resveratrol (RES)] and its two major metabolites, resveratrol-3-sulfate (R3S) … Continued

Microdialysis Evaluation of Clozapine and N-desmethylclozapine Pharmacokinetics in Rat Brain

By

A significant barrier to realization of the full potential of clozapine as a therapeutic agent in the treatment of schizophrenia is the substantial interpatient variability that exists along the therapeutic continuum of no response-efficacious response-adverse response. Genetic polymorphisms that manifest as highly variable pharmacodynamic and pharmacokinetic measures are its expected causes. To support investigations that … Continued

Pharmacokinetic and Pharmacodynamic Analysis of Efavirenz Dose Reduction Using an In Vitro-In Vivo Extrapolation Model

By

The pharmacokinetics (PK) of efavirenz (EFV) is characterized by marked inter-patient variability that correlates with its pharmacodynamics (PD). In vitro-in vivo extrapolation (IVIVE) is a “bottom-up” approach that combines drug data with system information to predict PK and PD. The aim of this study was to simulate EFV PK and PD after dose reductions. At … Continued

Relationship Between Prenatal Exposure to Polychlorinated Biphenyls and Birth Weight: A Systematic Analysis of Published Epidemiological Studies Through a Standardization of Biomonitoring Data

By

Impact of prenatal PCB exposure on birth weight was investigated in various children cohorts and findings of published studies show inconsistencies. Because a direct comparison of results obtained from different studies remains difficult, the “biological concentration-birth weight” relationship is not clearly established. The objective of this research was to perform a systematic analysis of published … Continued

2 of 2