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Jim Riviere

Publications and source records attributed to Jim Riviere.

5 recordsLinked to original sources
PubMed2006

Use of probabilistic modeling within a physiologically based pharmacokinetic model to predict sulfamethazine residue withdrawal times in edible tissues in swine.

The presence of antimicrobial agents in edible tissues of food-producing animals remains a major public health concern. Probabilistic modeling techniques incorporated into a physiologically based pharmacokinetic (PBPK) model were used to predict the amounts of sulfamethazine residues in edible tissues in swine. A PBPK model for sulfamethazine in swine was adapted to include an oral dosing route. The distributions for sensitive parameters were determined and were used in a Monte Carlo analysis to predict tissue residue times. Validation of the distributions was done by comparison of the results of a Monte Carlo analysis to those obtained with an external data set from the literature and an in vivo pilot study. The model was used to predict the upper limit of the 95% confidence interval of the 99th percentile of the population, as recommended by the U.S. Food and Drug Administration (FDA). The external data set was used to calculate the withdrawal time by using the tolerance limit algorithm designed by FDA. The withdrawal times obtained by both methods were compared to the labeled withdrawal time for the same dose. The Monte Carlo method predicted a withdrawal time of 21 days, based on the amounts of residues in the kidneys. The tolerance limit method applied to the time-limited data set predicted a withdrawal time of 12 days. The existing FDA label withdrawal time is 15 days. PBPK models can incorporate probabilistic modeling techniques that make them useful for prediction of tissue residue times. These models can be used to calculate the parameters required by FDA and explore those conditions where the established withdrawal time may not be sufficient.

Animals↗
PubMed2002

Applying the biopharmaceutics classification system to veterinary pharmaceutical products. Part II. Physiological considerations.

In comparing product bioavailability across animal species, it is not unusual to observe marked interspecies differences. For many compounds, these differences reflect presystemic drug metabolism. However, a host of other variables must also be considered such as in vivo drug solubility, gastric transit time, intestinal permeability, diet, and species-by-formulation interactions. By combining information on drug solubility and intestinal permeability with an understanding of the interrelationship between pH, product dissolution and gastrointestinal physiology, we attempt to define those conditions under which in vitro dissolution data may be used as a surrogate for data on in vivo bioavailability. We consider the likely physiological causes for species-related differences in the absolute and relative bioavailability of orally administered pharmaceuticals, and examine the potential for these normal interspecies differences to reflect bioavailability changes that can occur with various human pathologies.

Animal Feed↗
PubMedDate not supplied

Toxicokinetics and physiologically based toxicokinetics in toxicology and risk assessment.

Toxicokinetics is the study of kinetics of absorption, distribution, metabolism, and excretion of a xenobiotic under the conditions of toxicity evaluation. Conventional toxicokinetics uses the hypothetical compartments, and the model is composed of rate equations that describe the time course of drug and chemical disposition. The utility of toxicokinetics in toxicity evaluation and interpretation of animal toxicology data is emerging as an important tool in product discovery and development. With implementation of the International Conference on Harmonization (ICH) guidelines on systemic exposure and dose selection, toxicokinetics have been integrated in routine toxicity evaluations. Although traditional compartmental/noncompartmental models are generally adequate for assessing systemic exposure, they are unable to the predict time course of drug disposition in target tissues and often fail to relate systemic drug levels to a biological response. Physiologically based toxicokinetic (PB-TK) models address this deficiency of traditional compartmental models. PB-TK models are the kinetic models of the uptake and disposition of chemicals based on rates of biochemical reactions, physiological and anatomical characteristics. These models, when developed appropriately, can predict target organ drug distribution in different species under variety of conditions. This minireview discusses the basic principles, and applications of traditional compartmental toxicokinetic and physiologically based toxicokinetics (PB-TK) models in drug development and risk assessment. Special emphasis will be placed on discussion related to interpretation of the ICH guidelines related to toxicokinetics and the utility of toxicokinetics data in dose selection for toxicity and carcinogenicity studies. The utility of PB-TK models in risk assessment of methylene chloride, vinyl chloride, retinoic acid, dioxin, and inhaled organic esters is discussed.

Animals↗