Evaluation of deltamethrin kinetics and dosimetry in the maturing rat using a PBPK model.

Immature rats are more susceptible than adults to the acute neurotoxicity of pyrethroid insecticides like deltamethrin (DLM). A companion kinetics study (Kim et al., in press) revealed that blood and brain levels of the neuroactive parent compound were inversely related to age in rats 10, 21, 40 and 90 days old.

Pregnancy does not increase CYP3A or P-glycoprotein activity in the non-human primate, Macaca nemestrina.

Plasma concentrations of protease inhibitors are lower in pregnant women than in nonpregnant women or men. Using nelfinavir as a model protease inhibitor, we have shown that this phenomenon can be reproduced in a representative non-human primate model, Macaca nemestrina (J Pharmacol Exp Ther 329:1016-1022, 2009). Nelfinavir is cleared from the body predominantly by CYP3A metabolism and P-glycoprotein (P-gp) efflux.

As in humans, pregnancy increases the clearance of the protease inhibitor nelfinavir in the nonhuman primate Macaca nemestrina.

The apparent oral clearance of protease inhibitors (PIs) is increased in pregnant women. Although this phenomenon is reproduced in the mouse, because of the multiplicity of mouse cytochrome P450 isoforms, lack of information on their substrate and inhibitor selectivity, and lack of reagents (e.g.

Investigation on different levels of in vitro-in vivo correlation: gemfibrozil immediate release capsule.

Gemfibrozil is a practically water-insoluble, high-dose drug. It represents a typical drug with dissolution rate controlled bioavailability. The aim of this study was to select a dissolution condition for gemfibrozil immediate release capsules, resulting in the best in vitro/in vivo correlation (IVIVC).

Organ growth functions in maturing male Sprague-Dawley rats based on a collective database.

Ten different organ weights (liver, spleen, kidneys, heart, lungs, brain, adrenals, testes, epididymes, and seminal vesicles) of male Sprague-Dawley (S-D) rats of different ages (1-280 d) were extracted based on a thorough literature survey database. A generalized Michaelis-Menten (GMM) model, used to fit organ weights versus age in a previous study (Schoeffner et al., 1999) based on a limited data, was used to find the best fit model for the present expanded data compilation.

Organ growth functions in maturing male Sprague-Dawley rats.

Growth equations can be used in physiologically based pharmacokinetic (PBPK) modeling to provide physiological parameters (e.g., body weight, tissue/organ volumes) for maturing rodents.

Development of a physiologically based pharmacokinetic model for deltamethrin in the adult male Sprague-Dawley rat.

Deltamethrin (DLT) is a type II pyrethroid insecticide widely used in agriculture and public health. DLT is a potent neurotoxin that is primarily cleared from the body by metabolism. To better understand the dosimetry of DLT in the central nervous system, a physiologically based pharmacokinetic (PBPK) model for DLT was constructed for the adult, male Sprague-Dawley rat that employed both flow-limited (brain, gastrointestinal [GI] tract, liver, and rapidly perfused tissues) and diffusion-limited (fat, blood/plasma, and slowly perfused tissues) rate equations.

The effect of cimetidine on dextromethorphan O-demethylase activity of human liver microsomes and recombinant CYP2D6.

Clinically, cimetidine therapy impairs the clearance of various drugs metabolized by CYP2D6, such as desipramine and sparteine. Cimetidine is known to reversibly inhibit CYP2D6 in vitro; however, Ki values are greater than plasma concentrations observed in vivo. There is evidence suggesting that this drug may act as an inactivator of cytochrome P450 (P450) enzymes after metabolic activation.

A simple pharmacokinetics subroutine for modeling double peak phenomenon.

Double peak absorption has been described with several orally administered drugs. Numerous reasons have been implicated in causing the double peak. DRUG-KNT--a pharmacokinetic software developed previously for fitting one and two compartment kinetics using the iterative curve stripping method--was modified and a revised subroutine was incorporated to solve double-peak models.