Effects of pharmaceutical excipients on membrane permeability in rat small intestine

Takizawa, Yusuke; Kishimoto, Hisanao; Nakagawa, Minami; Sakamoto, Nasa; Tobe, Yoshifusa; Furuya, Takahito; Tomita, Mikio; Hayashi, Masahiro

doi:10.1016/j.ijpharm.2013.05.055

Cited by 30 publications

(26 citation statements)

References 23 publications

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“…16 Rats fasted overnight for 18 h were anesthetized using Somnopentyl R (pentobarbital sodium, 50 mg/kg, i.p. ), the abdomen was opened by making a midline longitudinal incision, and intestinal segments were removed from the duodenum, jejunum (5 cm below the Treitz ligament), ileum (5 cm above the cecum), and colon (5 cm below the cecum) in lengths of 4, 6, 6, and 4 cm, respectively.…”

Section: Drug Permeation Study Using the In Vitro Sac Methodsmentioning

confidence: 99%

Absorption-Enhancing Effect of Nitric Oxide on the Absorption of Hydrophobic Drugs in Rat Duodenum

Kishimoto

Miyazaki

Takizawa

et al. 2016

Journal of Pharmaceutical Sciences

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Nitric oxide (NO), an endogenous gas that plays a versatile role in the physiological system, has the ability to increase the intestinal absorption of water-soluble compounds through the paracellular route. However, it remains unclear whether NO can enhance the absorption of hydrophobic drugs through the transcellular route. In this study, we examined the absorption-enhancing effect of NO on intestinal permeability of hydrophobic drugs in rat intestine. The pretreatment of rat gastrointestinal sacs with NOC7, a NO-releasing reagent, significantly increased the permeation of griseofulvin from mucosa to serosa in the sacs prepared from the duodenum, but not in those prepared from the other regions such as jejunum, ileum, and colon. The absorption-enhancing effect of NOC7 on the duodenal permeation varied depending on the hydrophobicity of the drugs used. Furthermore, NOC7 treatment was found to be apparently ineffective on the griseofulvin permeation in the duodenum pretreated with dithiothreitol (DTT) that was used as a mucus remover, even though the permeation was increased by pretreatment with DTT alone. These results suggest that NO increases the absorption of hydrophobic drugs through the transcellular route in the duodenum by modulating the mucus layer function.

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Section: Drug Permeation Study Using the In Vitro Sac Methodsmentioning

confidence: 99%

Absorption-Enhancing Effect of Nitric Oxide on the Absorption of Hydrophobic Drugs in Rat Duodenum

Kishimoto

Miyazaki

Takizawa

et al. 2016

Journal of Pharmaceutical Sciences

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“…In a recent study, Takizawa et al (2013) investigated the influence of pharmaceutical excipients, such as microcrystalline cellulose (MCC), starch sodium glycolate (SSG), hydroxypropylmethyl cellulose (HPMC), ethyl cellulose (EC), and others on the membrane permeation of 5(6)-carboxyfluorescein (5-CF) in rat jejunum and ileum using the in vitro sac method. SSG significantly increased the membrane permeability of 5-CF in the jejunum, demonstrating that this polymer influences the intestinal efflux pump mechanism and enhances drug permeation.…”

Section: Resultsmentioning

confidence: 99%

“…The mucoadhesive properties of this polymer have been demonstrated in topical films and inhalant interactive mixtures that contain SSG (Repka, Mcginity, 2000;. Furthermore, it has been reported that SSG can function as a polymeric excipient with properties that inhibit the intestinal efflux mechanisms of drugs (Takizawa et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…Several studies have demonstrated that P-gp inhibitors (e.g., verapamil, VER) can improve the bioavailability of a large number of molecules (Werle, 2008;Ling et al, 2010). Takizawa et al (2013) demonstrated the effects of 20 common pharmaceutical excipients (diluents, disintegrants, binders, lubricants and sustained release substrate) on the mucosal membrane and how their effects differ in regions of the small intestine. The effects of these excipients on the membrane permeability of 5(6)-carboxyfluorescein (5-CF) were examined using the in vitro sac method in rat jejunum and ileum.…”

Section: Introductionmentioning

confidence: 99%

“…Studies have demonstrated that SSG and HPMCP enhance oral bioavailability through the inhibition of P-gp (CarrenoGomez, Duncan, 2001;Takizawa et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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A novel approach in mucoadhesive drug delivery system to improve zidovudine intestinal permeability

Pedreiro

Cury

Chaud

et al. 2016

Braz. J. Pharm. Sci.

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Zidovudine (AZT) mucoadhesive solid dispersions (SD) were prepared using a sodium starch glycolate (SSG) and hypromellose phthalate (HPMCP) mixtures as carrier to enhance the intestinal permeability and bioavailability of zidovudine. SDs were prepared using the co-precipitation method followed by solvent evaporation and characterized according to their physicochemical properties such as particle size, crystallinity, thermal behavior, and liquid uptake ability. In vitro drug dissolution, mucoadhesiveness and AZT intestinal permeability were also determined. Thermal behavior and X-ray diffraction patterns demonstrated the amorphous state of AZT in SD systems. The HPMCP polymer restricted the liquid uptake ability in the acid medium; however, this property significantly increased with higher pH values. SDs allowed drug dissolution to occur in a controlled manner. HPMCP decreased the dissolution rates in the acid medium. The mucoadhesiveness of SDs was demonstrated and the permeability of AZT carried in solid dispersions was significantly improved. The effect of the SD carrier polymers on blocking efflux pump can be an important approach to improve the bioavailability of AZT.Uniterms: Zidovudine. Solid dispersion. Mucoadhesion. P-glycoprotein. Intestinal permeability.

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Physiologically based pharmacokinetic modeling of tacrolimus for food–drug and CYP3A drug–drug–gene interaction predictions

Loer

Feick

Rüdesheim

et al. 2023

CPT Pharmacom & Syst Pharma

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The immunosuppressant and narrow therapeutic index drug tacrolimus is metabolized mainly via cytochrome P450 (CYP) 3A4 and CYP3A5. For its pharmacokinetics (PK), high inter‐ and intra‐individual variability can be observed. Underlying causes include the effect of food intake on tacrolimus absorption as well as genetic polymorphism in the CYP3A5 gene. Furthermore, tacrolimus is highly susceptible to drug–drug interactions, acting as a victim drug when coadministered with CYP3A perpetrators. This work describes the development of a whole‐body physiologically based pharmacokinetic model for tacrolimus as well as its application for investigation and prediction of (i) the impact of food intake on tacrolimus PK (food–drug interactions [FDIs]) and (ii) drug–drug(−gene) interactions (DD[G]Is) involving the CYP3A perpetrator drugs voriconazole, itraconazole, and rifampicin. The model was built in PK‐Sim® Version 10 using a total of 37 whole blood concentration–time profiles of tacrolimus (training and test) compiled from 911 healthy individuals covering the administration of tacrolimus as intravenous infusions as well as immediate‐release and extended‐release capsules. Metabolism was incorporated via CYP3A4 and CYP3A5, with varying activities implemented for different CYP3A5 genotypes and study populations. The good predictive model performance is demonstrated for the examined food effect studies with 6/6 predicted FDI area under the curve determined between first and last concentration measurements (AUClast) and 6/6 predicted FDI maximum whole blood concentration (Cmax) ratios within twofold of the respective observed ratios. In addition, 7/7 predicted DD(G)I AUClast and 6/7 predicted DD(G)I Cmax ratios were within twofold of their observed values. Potential applications of the final model include model‐informed drug discovery and development or the support of model‐informed precision dosing.

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Effects of pharmaceutical excipients on membrane permeability in rat small intestine

Cited by 30 publications

References 23 publications

Absorption-Enhancing Effect of Nitric Oxide on the Absorption of Hydrophobic Drugs in Rat Duodenum

Absorption-Enhancing Effect of Nitric Oxide on the Absorption of Hydrophobic Drugs in Rat Duodenum

A novel approach in mucoadhesive drug delivery system to improve zidovudine intestinal permeability

Physiologically based pharmacokinetic modeling of tacrolimus for food–drug and CYP3A drug–drug–gene interaction predictions

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