Differential Effect of Grapefruit Juice on Intestinal Absorption of Statins Due to Inhibition of Organic Anion Transporting Polypeptide and/or P-glycoprotein

Shirasaka, Yoshiyuki; Suzuki, Kensuke; Nakanishi, Takeo; Tamai, Ikumi

doi:10.1002/jps.22586

Cited by 65 publications

(40 citation statements)

References 44 publications

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“…Furthermore, Shirasaka et al reported that naringin, a component in GFJ, is the predominant molecule responsible for the inhibition of OATP2B1, while phloridzin and phloretin are the primary components contributing to inhibition of OATP2B1-mediated uptake in AJ [15]. Naringin has also been reported to inhibit P-gp [35,36], and P-gp significantly contributes to the pharmacokinetics of fexofenadine enantiomers [24,25,37]. Based on these previous studies, naringin in GFJ would be expected to inhibit both P-gp-and OATP2B1-mediated transport in relation to fexofenadine pharmacokinetics, and the reduced plasma concentrations of fexofenadine enantiomers in response to OATP2B1 inhibition may be attenuated by naringin-induced inhibition of P-gp, resulting in the observed differences between in vivo and in vitro results.…”

Section: Figmentioning

confidence: 94%

The change of pharmacokinetics of fexofenadine enantiomers through the single and simultaneous grapefruit juice ingestion

Akamine

Miura

Komori

et al. 2015

Drug Metabolism and Pharmacokinetics

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Section: Figmentioning

confidence: 94%

The change of pharmacokinetics of fexofenadine enantiomers through the single and simultaneous grapefruit juice ingestion

Akamine

Miura

Komori

et al. 2015

Drug Metabolism and Pharmacokinetics

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“…Fexofenadine absorption was reduced by ingestion with grapefruit juice by inhibition of OATP1A2 [58] or OATP2B1 [46]. Intestinal absorptions of statins [59], montelukast [49] and aliskiren [60] were reduced by inhibition of OATP2B1 by grapefruit juice. All these results support that OATPs are responsible for the drug-fruit juice interaction in the process of intestinal absorption.…”

Section: : Drug-fruit Juice Interaction On Oatp2b1mentioning

confidence: 98%

Oral drug delivery utilizing intestinal OATP transporters

Tamai

2012

Advanced Drug Delivery Reviews

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147

105

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Abstract.Transporters play important roles in tissue distribution and urinary-and biliary-excretion of drugs and transporter molecules involved in those processes have been elucidated well. Furthermore, an involvement of efflux transporters such as P-glycoproteins, multidrug resistance associated protein 2, and breast cancer resistance protein as the intestinal absorption barrier and/or intestinal luminal secretion mechanisms has been demonstrated. However, although there are many suggestions for the contribution of uptake/influx transporters in intestinal absorption of drugs, information on the transporter molecules responsible for the intestinal absorptive process is limited. Among them, most studied absorptive drug transporter is peptide transporter PEPT1. However, utilization of PEPT1 for oral delivery of drugs may not be high due to the chemical structural requirement of PEPT1 limited to peptide-mimetics. Recently, organic anion transporting polypeptide (OATP) family such as OATP1A2 and OATP2B1 has been suggested to mediate intestinal absorption of several drugs. Since OATPs exhibit species difference in expressed tissues and functional properties between human and animals, human studies are essential to clarify the intestinal absorption mechanisms of drugs via OATPs. Recent pharmacogenomics studies demonstrated that OATP2B1 is involved in the drug absorption in human. In addition, information of drug-juice interaction in the intestine also uncovered the contribution of OATP1A2 and OATP2B1 in drug absorption. Since OATP1A2 and OATP2B1 exhibit broader substrate selectivity compared with PEPT1, their potential to be applied for oral delivery should be high. In this review, current understanding of characteristics and contribution as the absorptive transporters of OATPs in small intestine in human is described. Now, it is getting clearer that OATPs have significant roles in intestinal absorption of drugs, therefore, there are higher possibility to utilize OATPs as the tools for oral delivery.

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“…However, pitavastatin absorption can be attenuated presystemically by P-glycoprotein (P-gp). 77,78 Finally, there is no reported transporter-mediated absorption influencing the simvastatin or lovastatin lactones.…”

Section: Absorptionmentioning

confidence: 99%

Pediatric Statin Administration: Navigating a Frontier with Limited Data

Wagner

Abdel‐Rahman

2016

The Journal of Pediatric Pharmacology and Therapeutics

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Increasingly, children and adolescents with dyslipidemia qualify for pharmacologic intervention. As they are for adults, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins) are the mainstay of pediatric dyslipidemia treatment when lifestyle modifications have failed. Despite the overall success of these drugs, the magnitude of variability in dose-exposure-response profiles contributes to adverse events and treatment failure. In children, the cause of treatment failures remains unclear. This review describes the updated guidelines for screening and management of pediatric dyslipidemia and statin disposition pathway to assist the provider in recognizing scenarios where alterations in dosage may be warranted to meet patients' specific needs.

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Differential Effect of Grapefruit Juice on Intestinal Absorption of Statins Due to Inhibition of Organic Anion Transporting Polypeptide and/or P-glycoprotein

Cited by 65 publications

References 44 publications

The change of pharmacokinetics of fexofenadine enantiomers through the single and simultaneous grapefruit juice ingestion

The change of pharmacokinetics of fexofenadine enantiomers through the single and simultaneous grapefruit juice ingestion

Oral drug delivery utilizing intestinal OATP transporters

Pediatric Statin Administration: Navigating a Frontier with Limited Data

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