The Effects of Food on the Bioavailability of Fenofibrate Administered Orally in Healthy Volunteers via Sustained-Release Capsule

Yun, Hyo-In; Chung, Soo Youn; Choi, Sun-Ok; Kim, Hyung Kee; Kwon, Jun-Tack; Kang, Wonku; Kwon, Kwang‐il

doi:10.2165/00003088-200645040-00007

Cited by 25 publications

(12 citation statements)

References 15 publications

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“…The subjects received a single nicotine patch (nicotine, 35 mg) after consuming a standard breakfast in the early morning of the experimental day. A transdermal patch was applied to a non-hairy, clean, dry site on the left upper arm and remained for 24 h. Blood samples (6 ml) and heart rate (HR) and blood pressure measurements were taken at 0, 1, 2, 4, 6, 8, 10, 12, 16, 24 (the elimination time of the patch), 25, 26, 28, 30 and 36 h. The blood samples were collected in heparinized tubes, immediately centrifuged (10 min, 3000 rpm), and stored at À801C until later analysis [11].…”

Section: Methodsmentioning

confidence: 99%

Effects of smoking on the pharmacokinetics and pharmacodynamics of a nicotine patch

Yun¹,

Seo²,

Choi³

et al. 2008

Biopharm & Drug Disp

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The effect of smoking on the pharmacokinetics and pharmacodynamics of a nicotine transdermal delivery system, administered as a single dose or multiple doses, was examined in smokers (n=12) and nonsmokers (n=12). The study was a two-period, parallel trial. In the first period, a single dose of the Nicotinell TTS 20 patch was administered, followed by a 1-week washout period. Then, in the second period, multiple doses of the Nicotinell TTS 20 patch were administered over 4 days. Regarding the pharmacokinetics of nicotine, the AUC(36 h) and AUC(tau) of smokers were about 20% and 40% greater, respectively, than those of nonsmokers. Significant differences in heart rate were observed between smokers and nonsmokers at 10, 12, 16 and 24 h, and significant differences in systolic blood pressure were seen between smokers and nonsmokers at 12, 30 and 36 h in the single-dose study. With multiple doses, significant differences in systolic and diastolic blood pressures were detected between smokers and nonsmokers only at 72.5 and 82 h. Here, it is demonstrated for the first time that the pharmacokinetic and hemodynamic effects of a nicotine patch are significantly different between smokers and nonsmokers.

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Section: Methodsmentioning

confidence: 99%

Effects of smoking on the pharmacokinetics and pharmacodynamics of a nicotine patch

Yun¹,

Seo²,

Choi³

et al. 2008

Biopharm & Drug Disp

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“…On the other hand, in humans, there appeared to be interindividual variability in PK, efficacy, and safety profiles of orally administered FF owing to the effect of food intake (Davidson et al, 2005). Yun et al (2006) demonstrated that the oral administration of FF with a high-fat meal can cause significant increases in C max and AUC 0-' of FA compared with those under fasted conditions in humans; hence, the effect of food intake, especially high-fat meals, might have a major effect on the photosafety of oral FF therapy since dermal exposure of FA might be increased when FF is orally taken with high-fat meals.…”

Section: Discussionmentioning

confidence: 99%

New Photosafety Assessment Strategy Based on the Photochemical and Pharmacokinetic Properties of Both Parent Chemicals and Metabolites

et al. 2015

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Photoreactivity and dermal/ocular deposition of compounds have been recognized as key considerations for evaluating the phototoxic risk of compounds. Because some drugs are known to cause phototoxic reactions via generation of potent phototoxic metabolites, photosafety assessments on parent drugs alone may lead to false predictions about their photosafety. This study aimed to establish a new photosafety assessment strategy for evaluating the in vivo phototoxic potential of both a parent substance and its metabolites. The in vivo phototoxic risk of fenofibrate (FF) and its metabolites, fenofibric acid (FA) and reduced fenofibric acid, were evaluated based on photochemical and pharmacokinetic analyses. FF and FA exhibited intensive UV absorption, with molar extinction coefficient values of 17,000 (290 nm) and 14,000 M 21 cm 21 (295 nm), respectively. Superoxide generation from FA was significantly higher than from FF, and a marked increase in superoxide generation from FF was observed after incubation with rat hepatic S9 fractions, suggesting enhanced photoreactivity of FF after metabolism. FA showed high dermal/ocular deposition after oral administration (5 mg/kg, p.o.) although the concentration of FF was negligible, suggesting high exposure risk from FA. On the basis of these findings, FA was deduced to be a major contributor to phototoxicity induced by FF taken orally, and this prediction was in accordance with the results from in vitro/in vivo phototoxicity tests. Results from this study suggest that this new screening strategy for parent substances and their metabolites provides reliable photosafety information on drug candidates and would be useful for drug development with wide safety margins.

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“…The physicochemical and biopharmaceutical properties of ibuprofen, ketoprofen, carvedilol, ketoconazole, danazol, and fenofibrate used in the GastroPlus™ simulations, as well as the chemical, physiological, and pharmacological parameters for drugs cited in the literature are presented in Table 1 (Abernethy and Greenblatt, 1985; Avdeef et al, 1998; Baxter et al, 1986; Beetge et al, 2000; Cordero et al, 1997; Domanska et al, 2009; Dressman and Lennernäs, 2000; Fei et al, 2013; Geisslinger et al, 1995; GlaxoSmithKline, 2009; Hooper et al, 1991; Huang et al, 1986; Ige et al, 2013; Kasim et al, 2004; Keating and Croom, 2007; Loftsson et al, 2008; Mannisto et al, 1982; Oliary et al, 1992; Peeters et al, 2008; Perez de la Cruz Moreno et al, 2006; Planinsek et al, 2011; Prajapati et al, 2012; Vertzoni et al, 2010; Yun et al, 2006). Since the size of drug particles can significantly affect drug dissolution rate, the relatively larger particle size, a radius of 25 μm, to minimize the particle effects for dissolution was set as the mean particle size with a coefficient of variation (Le et al, 2006; Lin et al, 1982; Mutalik et al, 2008; Sheng et al, 2008; Takano et al, 2008; Tsume and Amidon, 2010).…”

Section: Methodsmentioning

confidence: 99%

“… Vc; Volume of Central Compartment. A Calculated by GastroPlus™ 7.0. B Calculated by ADMET Predictor. a Oliary et al (1992). b Perez de la Cruz Moreno et al (2006). c Avdeef et al (1998). d Domanska et al (2009). e Abernethy and Greenblatt (1985). f Geisslinger et al (1995). g Cordero et al (1997). h Beetge et al (2000). i Kasim et al (2004). j GlaxoSmithKline (2009). k Planinsek et al (2011). l Loftsson et al (2008). m Huang et al (1986). n Vertzoni et al (2010). o Peeters et al (2008). p Mannisto et al (1982). q Baxter et al (1986). r Keating and Croom (2007). s Fei et al (2013). t Ige et al (2013). u Yun et al (2006). v Hooper et al (1991). w Prajapati et al (2012). x Dressman and Reppas (2000). …”

Section: Figmentioning

confidence: 99%

The Biopharmaceutics Classification System: Subclasses for in vivo predictive dissolution (IPD) methodology and IVIVC

Tsume

Mudie

Langguth

et al. 2014

European Journal of Pharmaceutical Sciences

281

169

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The Biopharmaceutics Classification System (BCS) has found widespread utility in drug discovery, product development and drug product regulatory sciences. The classification scheme captures the two most significant factors influencing oral drug absorption; solubility and intestinal permeability and it has proven to be a very useful and a widely accepted starting point for drug product development and drug product regulation. The mechanistic base of the BCS approach has, no doubt, contributed to its wide spread acceptance and utility. Nevertheless, underneath the simplicity of BCS are many detailed complexities, both in vitro and in vivo which must be evaluated and investigated for any given drug and drug product. In this manuscript we propose a simple extension of the BCS classes to include subspecification of acid (a), base (b) and neutral (c) for classes II and IV. Sub-classification for Classes I and III (high solubility drugs as currently defined) is generally not needed except perhaps in border line solubility cases. It is well known that the , pKa physical property of a drug (API) has a significant impact on the aqueous solubility dissolution of drug from the drug product both in vitro and in vivo for BCS Class II and IV acids and bases, and is the basis, we propose for a sub-classification extension of the original BCS classification. This BCS sub-classification is particularly important for in vivo predictive dissolution methodology development due to the complex and variable in vivo environment in the gastrointestinal tract, with its changing pH, buffer capacity, luminal volume, surfactant luminal conditions, permeability profile along the gastrointestinal tract and variable transit and fasted and fed states. We believe this sub-classification is a step toward developing a more science-based mechanistic in vivo predictive dissolution (IPD) methodology. Such a dissolution methodology can be used by development scientists to assess the likelihood of a formulation and dosage form functioning as desired in humans, can be optimized along with parallel human pharmacokinetic studies to set a dissolution methodology for Quality by Design (QbD) and in vitro–in vivo correlations (IVIVC) and ultimately can be used as a basis for a dissolution standard that will ensure continued in vivo product performance.

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The Effects of Food on the Bioavailability of Fenofibrate Administered Orally in Healthy Volunteers via Sustained-Release Capsule

Cited by 25 publications

References 15 publications

Effects of smoking on the pharmacokinetics and pharmacodynamics of a nicotine patch

Effects of smoking on the pharmacokinetics and pharmacodynamics of a nicotine patch

New Photosafety Assessment Strategy Based on the Photochemical and Pharmacokinetic Properties of Both Parent Chemicals and Metabolites

The Biopharmaceutics Classification System: Subclasses for in vivo predictive dissolution (IPD) methodology and IVIVC

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