scholarly journals Interaction of Oral Antidiabetic Drugs With Hepatic Uptake Transporters: Focus on Organic Anion Transporting Polypeptides and Organic Cation Transporter 1

Diabetes ◽  
2008 ◽  
Vol 57 (6) ◽  
pp. 1463-1469 ◽  
Author(s):  
I. Bachmakov ◽  
H. Glaeser ◽  
M. F. Fromm ◽  
J. Konig
Keyword(s):  
Organic Cation ◽  
Organic Anion ◽  
Organic Cation Transporter ◽  
Hepatic Uptake ◽  
Antidiabetic Drugs ◽  
Oral Antidiabetic Drugs ◽  
Organic Anion Transporting Polypeptides ◽  
Oral Antidiabetic ◽  
Organic Cation Transporter 1 ◽  
Uptake Transporters

scholarly journals Raltegravir Has a Low Propensity To Cause Clinical Drug Interactions through Inhibition of Major Drug Transporters: anIn VitroEvaluation

2013 ◽  
Vol 58 (3) ◽  
pp. 1294-1301 ◽  
Author(s):  
Matthew L. Rizk ◽  
Robert Houle ◽  
Grace Hoyee Chan ◽  
Mike Hafey ◽  
Elizabeth G. Rhee ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Organic Cation ◽  
Drug Transporters ◽  
Organic Anion ◽  
Organic Cation Transporter ◽  
Hepatic Uptake ◽  
Efflux Transporters ◽  
Renal Uptake ◽  
No Inhibition ◽  
Uptake Transporters

ABSTRACTRaltegravir (RAL) is a human immunodeficiency virus type 1 (HIV-1) integrase inhibitor approved to treat HIV infection in adults in combination with other antiretrovirals. The potential of RAL to cause transporter-related drug-drug interactions (DDIs) as an inhibitor has not been well described to date. In this study, a series ofin vitroexperiments were conducted to assess the inhibitory effects of RAL on major human drug transporters known to be involved in clinically relevant drug interactions, including hepatic and renal uptake transporters and efflux transporters. For hepatic uptake transporters, RAL showed no inhibition of organic anion-transporting polypeptide 1B1 (OATP1B1), weak inhibition of OATP1B3 (40% inhibition at 100 μM), and no inhibition of organic cation transporter 1 (OCT1). Studies of renal uptake transporters showed that RAL inhibited organic anion transporters 1 and 3 (OAT1 and OAT3) with 50% inhibitory concentrations (IC50s) (108 μM and 18.8 μM, respectively) well above the maximum concentration of drug in plasma (Cmax) at the clinical 400-mg dose and did not inhibit organic cation transporter 2 (OCT2). As for efflux transporters, RAL did not inhibit breast cancer resistance protein (BCRP) and showed weak inhibition of multidrug and toxin extrusion protein 1 (MATE1) (52% inhibition at 100 μM) and MATE2-K (29% inhibition at 100 μM). These studies indicate that at clinically relevant exposures, RAL does not inhibit or only weakly inhibits hepatic uptake transporters OATP1B1, OATP1B3, and OCT1, renal uptake transporters OCT2, OAT1, and OAT3, as well as efflux transporters BCRP, MATE1, and MATE2-K. The propensity for RAL to cause DDIs via inhibition of these transporters is therefore considered low.

scholarly journals Transporters in the Mammary Gland—Contribution to Presence of Nutrients and Drugs into Milk

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2372 ◽  
Author(s):  
García-Lino ◽  
Álvarez-Fernández ◽  
Blanco-Paniagua ◽  
Merino ◽  
Álvarez
Keyword(s):  
Mammary Gland ◽  
Organic Cation ◽  
Organic Anion ◽  
Environmental Pollutants ◽  
Organic Cation Transporter ◽  
Peptide Transporter ◽  
Cancer Resistance ◽  
Organic Anion Transporting Polypeptides ◽  
Organic Cation Transporter 1 ◽  
Bioactive Ingredients

A large number of nutrients and bioactive ingredients found in milk play an important role in the nourishment of breast-fed infants and dairy consumers. Some of these ingredients include physiologically relevant compounds such as vitamins, peptides, neuroactive compounds and hormones. Conversely, milk may contain substances—drugs, pesticides, carcinogens, environmental pollutants—which have undesirable effects on health. The transfer of these compounds into milk is unavoidably linked to the function of transport proteins. Expression of transporters belonging to the ATP-binding cassette (ABC-) and Solute Carrier (SLC-) superfamilies varies with the lactation stages of the mammary gland. In particular, Organic Anion Transporting Polypeptides 1A2 (OATP1A2) and 2B1 (OATP2B1), Organic Cation Transporter 1 (OCT1), Novel Organic Cation Transporter 1 (OCTN1), Concentrative Nucleoside Transporters 1, 2 and 3 (CNT1, CNT2 and CNT3), Peptide Transporter 2 (PEPT2), Sodium-dependent Vitamin C Transporter 2 (SVCT2), Multidrug Resistance-associated Protein 5 (ABCC5) and Breast Cancer Resistance Protein (ABCG2) are highly induced during lactation. This review will focus on these transporters overexpressed during lactation and their role in the transfer of products into the milk, including both beneficial and harmful compounds. Furthermore, additional factors, such as regulation, polymorphisms or drug-drug interactions will be described.

Involvement of organic anion-transporting polypeptides and organic cation transporter in the hepatic uptake of jatrorrhizine

Xenobiotica ◽  
2019 ◽  
Vol 50 (4) ◽  
pp. 479-487
Author(s):  
Rui-Feng Liang ◽  
Wen-Jing Ge ◽  
Xian-Mei Song ◽  
Jun-Ping Zhang ◽  
Wei-Feng Cui ◽  
...  
Keyword(s):  
Organic Cation ◽  
Organic Anion ◽  
Organic Cation Transporter ◽  
Hepatic Uptake ◽  
Organic Anion Transporting Polypeptides

scholarly journals Reduced Hepatic Uptake and Intestinal Excretion of Organic Cations in Mice with a Targeted Disruption of the Organic Cation Transporter 1 (Oct1 [Slc22a1]) Gene

2001 ◽  
Vol 21 (16) ◽  
pp. 5471-5477 ◽  
Author(s):  
Johan W. Jonker ◽  
Els Wagenaar ◽  
Carla A. A. M. Mol ◽  
Marije Buitelaar ◽  
Hermann Koepsell ◽  
...  
Keyword(s):  
Organic Cation ◽  
Basolateral Membrane ◽  
Organic Cation Transporter ◽  
Hepatic Uptake ◽  
Organic Cations ◽  
Wild Type ◽  
Targeted Disruption ◽  
Intestinal Excretion ◽  
Organic Cation Transporter 1

ABSTRACT The polyspecific organic cation transporter 1 (OCT1 [SLC22A1]) mediates facilitated transport of small (hydrophilic) organic cations. OCT1 is localized at the basolateral membrane of epithelial cells in the liver, kidney, and intestine and could therefore be involved in the elimination of endogenous amines and xenobiotics via these organs. To investigate the pharmacologic and physiologic role of this transport protein, we generated Oct1 knockout (Oct1 −/−) mice.Oct1 −/− mice appeared to be viable, healthy, and fertile and displayed no obvious phenotypic abnormalities. The role of Oct1 in the pharmacology of substrate drugs was studied by comparing the distribution and excretion of the model substrate tetraethylammonium (TEA) after intravenous administration to wild-type and Oct1 −/− mice. InOct1 −/− mice, accumulation of TEA in liver was four to sixfold lower than in wild-type mice, whereas direct intestinal excretion of TEA was reduced about twofold. Excretion of TEA into urine over 1 h was 53% of the dose in wild-type mice, compared to 80% in knockout mice, probably because inOct1 −/− mice less TEA accumulates in the liver and thus more is available for rapid excretion by the kidney. In addition, we found that absence of Oct1 leads to decreased liver accumulation of the anticancer drug metaiodobenzylguanidine and the neurotoxin 1-methyl-4-phenylpyridium. In conclusion, our data show that Oct1 plays an important role in the uptake of organic cations into the liver and in their direct excretion into the lumen of the small intestine.

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