Influene of Pharmaceutical Excipients on the Membrane Transport of a P-glycoprotein Substrate in the Rat Small Intestine

Takizawa, Yusuke; Goto, Nobuaki; Furuya, Takahito; Hayashi, Masahiro

doi:10.1007/s13318-020-00631-7

Cited by 7 publications

(5 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We previously identified croscarmellose sodium, lactose hydrate, magnesium stearate, and ethyl cellulose as pharmaceutical excipients that affect the membrane permeability of Rho123. 6 Furthermore, microcrystalline cellulose, Crospovidone. 18 Polysorbate 20.…”

Section: Discussionmentioning

confidence: 99%

“…Our research group investigated the effects of more than 20 pharmaceutical excipients on the membrane permeation of some compounds, which were the substrates for each permeation route, and demonstrated that many excipients affected the membrane permeation of compounds through both paracellular and transcellular pathways within the range of expected clinical doses. [4][5][6][7] Furthermore, they were shown to affect major drug transporters, such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). [8][9][10] Therefore, differences in the pharmaceutical excipients contained in tablets may affect gastrointestinal epithelial barrier function.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Comparison of a brand-name drug and its generic drugs - Impact of anti-human immunodeficiency virus drug exposure on the intestinal epithelial barrier

Takizawa,

Nagai,

Ishii

et al. 2024

Journal of Generic Medicines

Self Cite

View full text Add to dashboard Cite

The use of unapproved anti-human immunodeficiency virus (HIV) drugs for its treatment and prevention has recently increased in Japan. Our research group investigated generic drugs of the Truvada combination tablet (TVD) that have not been approved in Japan, and reported differences in the pharmaceutical properties of their formulations. We also demonstrated that the pharmaceutical excipients in generic drugs may differ from those in TVD, and showed that some pharmaceutical excipients may affect epithelial cell barrier function. The present study investigated differences in the effects of TVD and its generic drugs (Generic A and Generic B) on epithelial cell barrier function. No significant differences were observed in epithelial cell barrier function following exposure to TVD, Generic A, and Generic B. However, significant increases in the mRNA levels of ABCB1 and Occludin, which regulate the epithelial cell barrier, were detected following exposure to Generic B. Therefore, the administration of Generic B for a longer duration or at a higher concentration may lead to changes in epithelial barrier function. Since the treatment and prevention of HIV requires the long-term (chronic) administration of drugs, the drugs used may change, such as from a brand-name drug to a generic drug and also from one generic drug to another. The present results suggest that the effects of brand-name and generic drugs, such as on intestinal epithelial barrier function, may differ with changes in the drugs being administered.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparison of a brand-name drug and its generic drugs - Impact of anti-human immunodeficiency virus drug exposure on the intestinal epithelial barrier

Takizawa,

Nagai,

Ishii

et al. 2024

Journal of Generic Medicines

Self Cite

View full text Add to dashboard Cite

show abstract

“…Although the definition of a pharmaceutical excipient is "not to affect the efficacy of the main drug", pharmaceutical excipients may alter the membrane permeability of drugs. [5][6][7][8][9][10][11] There are also in vivo examples showing that differences between the brand name drug and its generic drug, such as brotizolam, 23 triazolam, 23 and pravastatin, 24 affected the onset and duration of drug efficacy. Based on these findings, differences in the excipients contained in Generic B and Truvada may change the absorption of the main drug and affect therapeutic effects.…”

Section: Discussionmentioning

confidence: 99%

“…Although the pharmaceutical excipients that form a pharmaceutical are generally considered to have no effect on the efficacy of a drug, our research group investigated the effects of more than 20 pharmaceutical excipients on the membrane permeation of some compounds and demonstrated that many excipients affected the membrane permeation of compounds through both paracellular and transcellular pathways, within the range of expected clinical doses. [5][6][7][8] Furthermore, their effects on major drug transporters, such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), have been reported. [9][10][11] Since the absorption ratio of FTC, which is the main component of Truvada, is as good as 92%, 12 it is considered to be less susceptible to various effects.…”

Section: Introductionmentioning

confidence: 99%

Comparison of pharmaceutical characteristics and membrane permeability of truvada combination tablets and its generic drugs

Takizawa,

Kunii,

Oguri

et al. 2023

Journal of Generic Medicines

Self Cite

View full text Add to dashboard Cite

Pre-exposure prophylaxis (PrEP) prevents HIV infection through the daily administration of anti-HIV drugs, such as Truvada combination tablets (a combination of emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF)). However, since PrEP is not approved in Japan, generic drugs sold overseas are imported and used by individuals. Then, the present study investigated the pharmaceutical equivalence of two generic drugs of Truvada (Generic A and Generic B). Tablet properties were examined by X-ray diffraction and differential scanning calorimetry. The dissolution behaviors and membrane permeabilities of FTC and TDF were assessed by the dissolution test using the paddle method and a membrane permeation experiment using Caco-2 cell monolayers, respectively. The dissolution behaviors of FTC and TDF differed between Truvada and its generic drugs. Furthermore, the membrane permeation rates of FTC and TDF in Generic B were slower than those in Truvada, and the AUC of FTC in Generic B was significantly smaller than that in Truvada. Differences were observed in the dissolution behaviors and membrane permeabilities of FTC and TDF in generic drugs (particularly Generic B) from those in Truvada. Since there are concerns regarding the clinical implications of these results, further studies, including in vivo experiments, are needed to ensure the safety of generic drugs.

show abstract

“…According to the International Coordination Committee for the Registration of Pharmaceutical Products for Human Use (ICH) guidelines and the M9 Bioequivalence Exemptions Based on the Biopharmaceutical Classification System [1][2][3][4] permeability is closely related to the rate and extent of drug absorption in the body and is one of the key factors in the transport of drugs in the body through expanded membranes and is relevant to drug development. Pharmaceutical excipients are non-physiologically active substances in pharmaceuticals that affect their absorption and bioavailability in the body [5][6][7]. For poorly permeable drugs, permeation enhancers are commonly used [8][9][10][11], for example, fatty alcohols, which increase drug permeability by altering the structure and properties of biofilms.…”

Section: Introductionmentioning

confidence: 99%

Decreased Penetration Mechanism of Ranitidine Due to Application of Sodium Sulfobutyl Ether-β-Cyclodextrin

Yang,

Zhang,

Huang

et al. 2023

Pharmaceutics

View full text Add to dashboard Cite

Permeability has an important effect on drug absorption. In this study, the effect of different concentrations of sodium sulfobutyl ether-β-cyclodextrin (SBE-β-CD) on the absorption of ranitidine was investigated to examine the mechanism of permeability changes. The results of a parallel artificial membrane permeability assay (PAMPA) showed that increasing the concentration of sodium sulfobutyl ether-β-cyclodextrin, 0, 0.12% (w/v), 0.36% (w/v) and 3.6% (w/v), respectively, caused the apparent permeability coefficient of ranitidine to decrease to 4.62 × 10−5, 4.5 × 10−5, 3.61 × 10−5 and 1.08 × 10−5 in Caco-2 cells, respectively. The same results were obtained from an oral pharmacokinetic study in rats. Further studies indicated that SBE-β-CD significantly increased the zeta potential of ranitidine. SBE-β-CD interacted with ranitidine charges to form a complex that reduced ranitidine permeability, and SBE-β-CD should be chosen with caution for drugs with poor permeability.

show abstract

Influene of Pharmaceutical Excipients on the Membrane Transport of a P-glycoprotein Substrate in the Rat Small Intestine

Cited by 7 publications

References 26 publications

Comparison of a brand-name drug and its generic drugs - Impact of anti-human immunodeficiency virus drug exposure on the intestinal epithelial barrier

Comparison of a brand-name drug and its generic drugs - Impact of anti-human immunodeficiency virus drug exposure on the intestinal epithelial barrier

Comparison of pharmaceutical characteristics and membrane permeability of truvada combination tablets and its generic drugs

Decreased Penetration Mechanism of Ranitidine Due to Application of Sodium Sulfobutyl Ether-β-Cyclodextrin

Contact Info

Product

Resources

About