Prediction of diazepam disposition in the rat and man by a physiologically based pharmacokinetic model

Igari, Yasutaka; Sugiyama, Yuichi; Sawada, Yasufumi; Iga, Tatsuji; Hanano, Manabu

doi:10.1007/bf01059058

Cited by 103 publications

(62 citation statements)

References 27 publications

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“…Tissue:blood partition coefficients for nonvolatile chemicals may be estimated in vitro using radioactive chemicals in ultrafiltration, equilibrium dialysis or vial equilibration procedures (Lin et al, 1982;Igari et al, 1983;Sultatos et al, 1990;Jepson et al, 1994;Murphy et al, 1995). The partition coefficients estimated by these in vitro methods are acceptable, provided equilibrium is attained during the experimental conditions.…”

Section: Partition Coefficientsmentioning

confidence: 99%

Evaluation of physiologically based pharmacokinetic models for use in risk assessment

Chiu

Barton

DeWoskin

et al. 2007

J of Applied Toxicology

139

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Physiologically based pharmacokinetic (PBPK) models are sophisticated dosimetry models that offer great flexibility in modeling exposure scenarios for which there are limited data. This is particularly of relevance to assessing human exposure to environmental toxicants, which often requires a number of extrapolations across species, route, or dose levels. The continued development of PBPK models ensures that regulatory agencies will increasingly experience the need to evaluate available models for their application in risk assessment. To date, there are few published criteria or well-defined standards for evaluating these models. Herein, important considerations for evaluating such models are described. The evaluation of PBPK models intended for risk assessment applications should include a consideration of: model purpose, model structure, mathematical representation, parameter estimation, computer implementation, predictive capacity and statistical analyses. Model purpose and structure require qualitative checks on the biological plausibility of a model. Mathematical representation, parameter estimation, computer implementation involve an assessment of the coding of the model, as well as the selection and justification of the physical, physicochemical and biochemical parameters chosen to represent a biological organism. Finally, the predictive capacity and sensitivity, variability and uncertainty of the model are analysed so that the applicability of a model for risk assessment can be determined. Published in 2007 by John Wiley & Sons, Ltd.

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Section: Partition Coefficientsmentioning

confidence: 99%

Evaluation of physiologically based pharmacokinetic models for use in risk assessment

Chiu

Barton

DeWoskin

et al. 2007

J of Applied Toxicology

139

View full text Add to dashboard Cite

show abstract

“…This technique involves determining the headspace concentration of the chemical in test vials containing the tissues of interest and comparing the concentration measured to appropriate reference vials. Partition coefficients for nonvolatile xenobiotics can be determined in vitro using equilibrium dialysis or ultrafiltration techniques [Lin et al, 1982;Igari et al, 1983;Jepson, 1986;Fisher et al, 1990. Biochemical parameters required for modeling are mainly metabolic rate constants, which can be determined either in vivo or in vitro. Two innovative methods have been devised for estimation of the metabolic rate constants of volatile organic chemicals.…”

Section: Physiological Modelingmentioning

confidence: 99%

Physiological Modeling and Cancer Risk Assessment

Krishnan

Andersen

1991

New Trends in Pharmacokinetics

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“…The Kp values were assumed to be identical among mammals. The organ and tissue volumes and blood flow rates for humans that were used in the global PB-PK model were obtained from the literature (3,10,14,18,24,38) and are presented in Table 1.…”

Section: Methodsmentioning

confidence: 99%

Physiologically Based Pharmacokinetic Model for Terbinafine in Rats and Humans

Hosseini-Yeganeh

McLachlan

2002

Antimicrob Agents Chemother

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The aim of this study was to develop a physiologically based pharmacokinetic (PB-PK) model capable of describing and predicting terbinafine concentrations in plasma and tissues in rats and humans. A PB-PK model consisting of 12 tissue and 2 blood compartments was developed using concentration-time data for tissues from rats (n ‫؍‬ 33) after intravenous bolus administration of terbinafine (6 mg/kg of body weight). It was assumed that all tissues except skin and testis tissues were well-stirred compartments with perfusion rate limitations. The uptake of terbinafine into skin and testis tissues was described by a PB-PK model which incorporates a membrane permeability rate limitation. The concentration-time data for terbinafine in human plasma and tissues were predicted by use of a scaled-up PB-PK model, which took oral absorption into consideration. The predictions obtained from the global PB-PK model for the concentration-time profile of terbinafine in human plasma and tissues were in close agreement with the observed concentration data for rats. The scaled-up PB-PK model provided an excellent prediction of published terbinafine concentration-time data obtained after the administration of single and multiple oral doses in humans. The estimated volume of distribution at steady state (V ss ) obtained from the PB-PK model agreed with the reported value of 11 liters/kg. The apparent volume of distribution of terbinafine in skin and adipose tissues accounted for 41 and 52%, respectively, of the V ss for humans, indicating that uptake into and redistribution from these tissues dominate the pharmacokinetic profile of terbinafine. The PB-PK model developed in this study was capable of accurately predicting the plasma and tissue terbinafine concentrations in both rats and humans and provides insight into the physiological factors that determine terbinafine disposition.Terbinafine is an antifungal agent from the allylamine class that inhibits the fungal squalene epoxidase enzyme, leading to the intracellular accumulation of squalene, which causes the rapid death of fungi (36,37). It has demonstrated activity against most superficial fungal infections, including onychomycosis and dermatomycosis (11,17), and systemic fungal infections, such as histoplasmosis (1), Pneumocystis carinii infection, (8), and aspergillosis (39). Terbinafine is highly lipophilic and keratophilic, so it is extensively distributed throughout adipose tissue, dermis, epidermis, and nails in humans (12,19). The apparent volume of distribution in humans is relatively large and has been reported to be in the range of 780 to 2,000 liters (22,25,27,28,33). The large volume of distribution of terbinafine and its accumulation in peripheral tissue as well as the slow redistribution of the drug into blood are likely to significantly influence the half-life of terbinafine. Previous studies have variously reported the elimination half-life of terbinafine in humans to be 15 h (33), 26 h (27), 290 h (35), and 22 days (33,35,43). Terbinafine is extensively metabolize...

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Prediction of diazepam disposition in the rat and man by a physiologically based pharmacokinetic model

Cited by 103 publications

References 27 publications

Evaluation of physiologically based pharmacokinetic models for use in risk assessment

Evaluation of physiologically based pharmacokinetic models for use in risk assessment

Physiological Modeling and Cancer Risk Assessment

Physiologically Based Pharmacokinetic Model for Terbinafine in Rats and Humans

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