Predicting Effect of Food on Extent of Drug Absorption Based on Physicochemical Properties

Gu, Chong‐Hui; Li, Hua; Levons, Jaquan K.; Lentz, Kimberley A.; Gandhi, Rajesh B.; Raghavan, Krishnaswamy; Smith, Ronald L.

doi:10.1007/s11095-007-9236-1

Cited by 144 publications

(81 citation statements)

References 95 publications

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“…0 -2 range. This theoretical finding is in good agreement with the physicochemical property -food effect relationship in [65] [66].…”

Section: General Absorption Equationsupporting

confidence: 86%

Computational Oral Absorption Simulation for Low‐Solubility Compounds

Sugano

2009

Chemistry & Biodiversity

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Bile micelles play an important role in oral absorption of low-solubility compounds. Bile micelles can affect solubility, dissolution rate, and permeability. For the pH-solubility profile in bile micelles, the Henderson-Hasselbalch equation should be modified to take bile-micelle partition into account. For the dissolution rate, in the Nernst-Brunner equation, the effective diffusion coefficient in bile-micelle media should be used instead of the monomer diffusion coefficient. The diffusion coefficient of bile micelles is 8- to 18-fold smaller than that of monomer molecules. For permeability, the effective diffusion coefficient in the unstirred water layer adjacent to the epithelial membrane, and the free fraction at the epithelial membrane surface should be taken into account. The importance of these aspects is demonstrated here using several in vivo and clinical oral-absorption data of low-solubility model compounds. Using the theoretical equations, the food effect on oral absorption is further discussed.

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“…0 -2 range. This theoretical finding is in good agreement with the physicochemical property -food effect relationship in [65] [66].…”

Section: General Absorption Equationsupporting

confidence: 86%

Computational Oral Absorption Simulation for Low‐Solubility Compounds

Sugano

2009

Chemistry & Biodiversity

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“…16) The maximum absorbable dose (MAD) of 92 drugs was calculated using solubility, fluid volume (250 ml), transit time (180 min) and absorption rate constant (min…”

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confidence: 99%

In Vitro Dissolution/Permeation System to Predict the Oral Absorption of Poorly Water-Soluble Drugs: Effect of Food and Dose Strength on It

Kataoka

Itsubata

Masaoka

et al. 2011

Biological & Pharmaceutical Bulletin

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The oral absorption of drugs and drug candidates often varies, when they are administered after food intake.1-4) The effect of food on oral drug absorption may alter the effectiveness of drug therapy. Thus, dosing instructions should be carefully set on the basis of the characteristics of drug absorption in order to ensure a high level of effectiveness in drug therapy. The oral drug absorption under the fed state can be more or less than that under the fasted state, which are often called positive and negative food effects, respectively. [5][6][7][8] Fleisher et al. stated that drugs classified into class I, class II and class III using the biopharmaceutics classification system (BCS) are likely to be not affected by food, be positively affected by food and be negatively affected by food, respectively, while the effects are unclear for class IV drugs. 9)As the main cause of the positive food effect, it is considered that the ingestion of food stimulates the secretion of bile juice into the gastrointestinal tract, which accelerates the solubility and dissolution of poorly water-soluble drugs and then enhances oral absorption. [10][11][12] The oral absorption of drugs with high lipophilicity was affected by the food state, which is shown in Table 1. For instance, the oral absorption of albendazole was enhanced 4-fold by the intake of food. However, the total absorbed amount of nateglinide was the almost same between the fasted and fed states because the intake of food did not enhance area under curve (AUC) but induced a decreased absorption rate (decreased C max and prolonged T max ).13) Moreover, the oral absorption of poorly water-soluble drugs is often proportionally reduced with increasing dose strength owing to solubility-and dissolution rate-limited absorption.14,15) Thus, these effects on drug absorption should be considered when the oral absorption of poorly water-soluble drugs is predicted.Gu et al. proposed a statistical model for prediction of the effect of food on drug absorption.16) The maximum absorbable dose (MAD) of 92 drugs was calculated using solubility, fluid volume (250 ml), transit time (180 min) and absorption rate constant (min Ϫ1). Then, the effect of food on drug absorption was predicted by comparing MAD with clinical dose and using logistic regression with physicochemical properties. For the 92 drugs, 80% were correctly categorized into positive, negative or no effect of food groups in the prediction. In the case of a positive effect of food, 83% were successfully classified. Although the adapted method is useful for the qualitative prediction of the effect of food on drug absorption, it may not be suitable for its quantitative prediction.In previous studies, we developed an in vitro system (Dissolution/Permeation system: D/P system, Fig. 1) to evaluate the dissolution and permeation of drugs in solid dosage form.17) The D/P system enables simultaneous determination of drug dissolution and permeation after a drug is applied to the apical side of the system. The applied amount of drugs wa...

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“…Changes in exposure with food for a BCS Class 4 compound can be challenging to predict [15], although an analysis of more than 90 compounds indicated a tendency toward a positive food eVect for the subset of BCS Class 4 compounds entered into the analysis [16]. In Table 1 Summary of blood pharmacokinetic parameter values following the administration of a single 40-mg oral rose of ridaforolimus in the fasted and fed states (fasted, light, and high fat) in healthy young male subjects a Back-transformed least squares mean and conWdence interval from mixed-eVects model performed on natural log-transformed values b rMSE Square root of conditional mean squared error (residual error) from the linear mixed-eVect model.…”

Section: Discussionmentioning

confidence: 99%