Intestinal Absorption of Alogliptin Is Mediated by a Fruit-Juice-Sensitive Transporter

Morimoto, Kaori; Sasaki, Momona; Oikawa, Erika; Abe, Matanobu; Kikuchi, Tetsuro; Ishii, Makoto; Ogihara, Takuo; Tomita, Mikio

doi:10.1248/bpb.b20-00947

Cited by 3 publications

(3 citation statements)

References 19 publications

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“…The mechanisms for the uptake and excretion of drugs across cell membranes include simple diffusion and transportermediated transport. AG has a molecular weight of 339.39 and a low lipophilicity (log P = −1.4) [18], which makes it difficult to pass through the cell membrane by simple diffusion. This suggests the involvement of transporters.…”

Section: Discussionmentioning

confidence: 99%

“…To the best of our knowledge, only one report by Morimoto et al suggests the involvement of transporters for AG, which mentions that although AG is a cationic drug, AG uptake into Caco-2 cells was significantly inhibited by the organic anion transporting polypeptide (OATP) substrate and by the OATP inhibitor, but was not inhibited by organic cation transporter (OCT), organic cation/carnitine transporter (OCTN), or peptide transporter 1 (PEPT1) substrates [18].…”

Section: Discussionmentioning

confidence: 99%

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Immunohistochemical Localization of Alogliptin, a DPP-4 Inhibitor, in Tissues of Normal and Type 2 Diabetes Model Rat

Yamamoto

Ura

Matsukawa

et al. 2022

Acta Histochem. Cytochem

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We investigated the pharmacokinetics of alogliptin (AG) at the cell and tissue level in healthy Wistar rats and a type 2 diabetic Goto-Kakizaki (GK) rat model. Immunohistochemistry of the renal tissue in these rats, post 1 hr of AG administration, showed that the signal was observed in the glomeruli, proximal tubule S3 segments, distal tubules, collecting ducts, and only in the brush border of the epithelial cells of the proximal tubule S1, S2 segments. After 6 hr of AG administration, the staining intensity of the regions other than the S3 segments was considerably reduced in Wistar rats, with no change observed in GK rats. At 24 hr, the staining intensity was considerably reduced, even in GK rats; however, the staining of the S3 segment remained unaltered in both. Hepatocytes in zone III of the hepatic lobule were more intensely stained than those in zone I in Wistar rats at 1 hr. However, almost no staining was observed in the hepatocytes of GK rats at 1 hr. Complete loss of signal was observed in the hepatocytes of the Wistar rats after 6 hr. This study revealed that the pharmacokinetics of AG in GK rats are different from those in Wistar rats.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Localization of Alogliptin, a DPP-4 Inhibitor, in Tissues of Normal and Type 2 Diabetes Model Rat

Yamamoto

Ura

Matsukawa

et al. 2022

Acta Histochem. Cytochem

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“…The drug was mediated by some transporters which are sensitive to fruit juice in intestine. This would result in inhibiting intestinal adsorption of Alogliptin (Morimoto et al, 2021).…”

Section: Alogliptinmentioning

confidence: 99%

Opportunities and challenges of incretins-based hypoglycemic agents treating of T2DM from the insight of physiological disposition

Xie,

He,

Wang

et al. 2024

Preprint

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The treatment on patients with T2DM who suffered from defective in insulin secretion and inability of tissues responding to insulin properly have been studied for decades. Currently, incretins-based hypoglycemic agents have become a focus in treating T2DM and this kind of drugs could be classified as GLP-1 receptor agonists which mimic the function of GLP-1 and DPP-4 antagonists which avoid GLP-1 being degraded. Both of them focused on GLP-1 polypeptide. Since incretins-based hypoglycemic agents are widely used, the physiological disposition is of great significance in discovering more effective drugs and providing guidance on clinicals for treating T2DM. In the review, we summarize the mechanisms of these two kinds of drugs and provide information of the drugs currently be approved. In addition, the physiological disposition of each type of GLP-1 receptor agonists and DPP-4 antagonists are thoroughly reviewed. By this review, based on the physiological disposition of these drugs, patients with different situation could choose the drugs based on their physical conditions and the need of supplementary treatment in avoid of drug interactions. We also hope some drugs with novel structure with appropriate physiological disposition could be inspired and invented.

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Opportunities and challenges of incretin-based hypoglycemic agents treating type 2 diabetes mellitus from the perspective of physiological disposition

Xie¹,

Zhou²,

He³

et al. 2023

Acta Pharmaceutica Sinica B

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Intestinal Absorption of Alogliptin Is Mediated by a Fruit-Juice-Sensitive Transporter

Cited by 3 publications

References 19 publications

Immunohistochemical Localization of Alogliptin, a DPP-4 Inhibitor, in Tissues of Normal and Type 2 Diabetes Model Rat

Immunohistochemical Localization of Alogliptin, a DPP-4 Inhibitor, in Tissues of Normal and Type 2 Diabetes Model Rat

Opportunities and challenges of incretins-based hypoglycemic agents treating of T2DM from the insight of physiological disposition

Opportunities and challenges of incretin-based hypoglycemic agents treating type 2 diabetes mellitus from the perspective of physiological disposition

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