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A level A in vitro/in vivo correlation in fasted and fed states using different methods: Applied to solid immediate release oral dosage form

Equipe de Recherche Technologique, Conception, Ingénierie et Développement de l'Aliment et du Médicament (ERT CIDAM), groupe biopharmaceutique, Faculté de pharmacie, 28 place Henri Dunant, 63000 Clermont-Ferrand, France.
European Journal of Pharmaceutical Sciences (Impact Factor: 3.35). 02/2006; 27(1):72-9. DOI: 10.1016/j.ejps.2005.08.006
Source: PubMed

ABSTRACT

The first purpose of this study was to simulate the impact of food intake on drug release and absorption in vivo using a novel in vitro system which mimics the gastro-intestinal (GI) tract in man. The drug studied was acetaminophen in the form of immediate release (IR) tablets. The second purpose was to establish a level A in vitro/in vivo correlation that could predict the bioavailability of a drug instead of using difficult, time-consuming and expensive in vivo bioequivalence studies. The artificial digestive system was used to estimate the availability of acetaminophen IR tablets for absorption in fasted and fed states. The same study was performed in vivo under similar conditions. A comparison study was carried out between the classical and the novel methods to estimate the efficacy of the new in vitro system to simulate the influence of food on drug release and absorption in vivo. A level A in vitro/in vivo correlation was established with a correlation coefficient of 0.9128 and 0.9984 in the fasted and fed states, respectively. Compared to USP II method, the novel in vitro model demonstrated a high level of efficacy in mimicking the behaviour of acetaminophen IR tablets in vivo in fasted and fed states.

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Available from: Stéphanie Blanquet-Diot, Oct 31, 2014
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    • "The TIM-1 system (TNO In-vitro gastro-intestinal Model) is a unique, validated, computer-controlled simulation of the stomach and small intestine with great reproducibility and application in studies of human health (Minekus et al., 1995, Minekus, 1998; Souliman et al., 2006). A detailed description of the TIM-1 system and methodology has been previously reported (Blanquet et al., 2004; Minekus et al., 2005; Faessler et al., 2006). "
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    ABSTRACT: Objectives Bioaccessibility is a useful measure for assessing the biological value of a particular nutrient from food, especially foods such as tubers. The wild tubers exploited by Hadza foragers in Tanzania are of interest because they are nontoxic, consumed raw or briefly roasted, and entail substantial physical barriers to consumers. In this study, we attempted to elucidate the biological value of Hadza tubers by measuring the absorption of glucose through in-vitro digestion. Methods We quantified digestibility using data from 24 experimental trials on four species of Hadza tuber using a dynamic in-vitro model that replicates digestion in the stomach and small intestine. Analysis of glucose in the input meal and output dialysate revealed the accessible glucose fraction. We also conducted assays for protein, vitamin, and mineral content on whole tubers and meal fractions. Results Bioaccessibility of glucose varies depending on tuber species. Holding effects of chewing constant, brief roasting had negligible effects, but high intraspecific variation precludes interpretive power. Overall, Hadza tubers are very resistant to digestion, with between one- and two-thirds of glucose absorbed on average. Glucose absorption negatively correlated with glucose concentration of the tubers. Conclusions Roasting may provide other benefits such as ease of peeling and chewing to extract edible parenchymatous tissue. A powerful factor in glucose acquisition is tuber quality, placing emphasis on the skill of the forager. Other nutrient assays yielded unexpectedly high values for protein, iron, and iodine, making tubers potentially valuable resources beyond caloric content.
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    • "Next, model predictions of APAP absorption into the bloodstream were assessed. Figure 5shows simulated values of the cumulative fraction absorbed (CFA), along with corresponding in vivo data fromSouliman et al. (2006), for a 500-mg oral dose of APAP administered to humans in a fasted state. The good agreement between model predictions and experimental data lends support to the quantitative description of absorption used in the PBPK model. "
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    ABSTRACT: The principal aim of this study was to develop, validate, and demonstrate a physiologically based pharmacokinetic (PBPK) model to predict and characterize the absorption, distribution, metabolism, and excretion of acetaminophen (APAP) in humans. A PBPK model was created that included pharmacologically and toxicologically relevant tissue compartments and incorporated mechanistic descriptions of the absorption and metabolism of APAP, such as gastric emptying time, cofactor kinetics, and transporter-mediated movement of conjugated metabolites in the liver. Through the use of a hierarchical Bayesian framework, unknown model parameters were estimated using a large training set of data from human pharmacokinetic studies, resulting in parameter distributions that account for data uncertainty and inter-study variability. Predictions from the model showed good agreement to a diverse test set of data across several measures, including plasma concentrations over time, renal clearance, APAP absorption, and pharmacokinetic and exposure metrics. The utility of the model was then demonstrated through predictions of cofactor depletion, dose response of several pharmacokinetic endpoints, and the relationship between APAP biomarker levels in the plasma and those in the liver. The model addressed several limitations in previous PBPK models for APAP, and it is anticipated that it will be useful in predicting the pharmacokinetics of APAP in a number of contexts, such as extrapolating across doses, estimating internal concentrations, quantifying population variability, assessing possible impacts of drug coadministration, and, when coupled with a suitable pharmacodynamic model, predicting toxicity.
    Full-text · Article · Jan 2015 · European Journal of Drug Metabolism and Pharmacokinetics
    • "For conventional drug and nutritional compounds, TIM-1 has been extensively used to characterize their bioaccessibility from food and beverage product matrices, expressed as a percentage intake, under various physiological conditions and transit times along the GI tract (Blanquet et al., 2004). The profiles are highly consistent with preclinical jejunal data in both fasted and fed states (Souliman et al., 2006). "

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