Abstract
The kidneys are a pair of important organs that excretes endogenous waste and exogenous biological agents from the body. Numerous transporters are involved in the excretion process. The levels of these transporters could affect the pharmacokinetics of many drugs, such as organic anion drugs, organic cationic drugs, and peptide drugs. Eleven drug transporters in the kidney (OAT1, OAT3, OATP4C1, OCT2, MDR1, BCRP, MATE1, MATE2-K, OAT4, MRP2, and MRP4) have become necessary research items in the development of innovative drugs. However, the levels of these transporters vary between different species, sex-genders, ages, and disease statuses, which may lead to different pharmacokinetics of drugs. Here, we review the differences of the important transports in the mentioned conditions, in order to help clinicians to improve clinical prescriptions for patients. To predict drug-drug interactions (DDIs) caused by renal drug transporters, the molecular docking method is used for rapid screening of substrates or inhibitors of the drug transporters. Here, we review a large number of natural products that represent potential substrates and/or inhibitors of transporters by the molecular docking method.
Highlights
The kidneys are the main excretory organs of the body, which play key roles in excretion of metabolites, acid-base balance, and homeostasis of the body system
It is difficult to investigate the changes of drug transporters in the human kidney throughout life, an age-related study on OAT1, OAT3, organic anion transporter polypeptide 4C1 (OATP4C1), OCT2, MDR1, breast cancer resistance protein (BCRP), MATE1, MATE2-K, multidrug resistanceassociated protein 2 (MRP2), and MRP4 mRNA expressions was performed in male rat kidneys with quantitative real time-polymerase chain reaction (qPCR) and Western blot methods (Xu et al, 2017)
Most renal drug transporters are not affected by a long-term administration of a high-fat diet, but decreased expressions of the uptake protein OAT1/3 was observed in the kidney (Lu et al, 2019), which can lead to an accumulation of endogenous toxic substances that may contribute to obesity-related diseases, such as hyperlipidemia, nonalcoholic fatty liver disease (NAFLD), chronic kidney disease (CKD), and diabetes
Summary
The kidneys are the main excretory organs of the body, which play key roles in excretion of metabolites, acid-base balance, and homeostasis of the body system. Impacts on 11 drug transporters in the kidneys, including OAT1, OAT3, organic anion transporter polypeptide 4C1 (OATP4C1), organic cation transporter (OCT2), multidrug resistance protein 1 [MDR1, namely p-glycoproteins (P-gp)], breast cancer resistance protein (BCRP), MATE1, MATE2-K, OAT4, multidrug resistanceassociated protein 2 (MRP2), and MRP4, have become necessary research items in the development of innovative drugs (Food and Drug Administration, 2020). These drug transporters are mainly distributed on the basolateral membrane and apical membrane of renal proximal tubular cells, which are shown in Table 1 and Figure 1. The molecular docking technology applied on renal drug transporters was reviewed, which could facilitate
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