Intestinal Drug Interactions Mediated by OATPs: A Systematic Review of Preclinical and Clinical Findings.
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Yu J, Zhou Z, Tay-Sontheimer J, Levy RH, Ragueneau-Majlessi I
Intestinal Drug Interactions Mediated by OATPs: A Systematic Review of Preclinical and Clinical Findings.
J Pharm Sci. 2017 Sep;106(9):2312-2325. doi: 10.1016/j.xphs.2017.04.004. Epub 2017 Apr 13.
- PubMed ID
- 28414144 [ View in PubMed]
- Abstract
In recent years, an increasing number of clinical drug-drug interactions (DDIs) have been attributed to inhibition of intestinal organic anion-transporting polypeptides (OATPs); however, only a few of these DDI results were reflected in drug labels. This review aims to provide a thorough analysis of intestinal OATP-mediated pharmacokinetic-based DDIs, using both in vitro and clinical investigations, highlighting the main mechanistic findings and discussing their clinical relevance. On the basis of pharmacogenetic and clinical DDI results, a total of 12 drugs were identified as possible clinical substrates of OATP2B1 and OATP1A2. Among them, 3 drugs, namely atenolol, celiprolol, and fexofenadine, have emerged as the most sensitive substrates to evaluate clinical OATP-mediated intestinal DDIs when interactions with P-glycoprotein by the test compound can be ruled out. With regard to perpetrators, 8 dietary or natural products and 1 investigational drug, ronacaleret (now terminated), showed clinical intestinal inhibition attributable to OATPs, producing >/=20% decreases in area under the plasma concentration-time curve of the co-administered drug. Common juices, such as apple juice, grapefruit juice, and orange juice, are considered potent inhibitors of intestinal OATP2B1 and OATP1A2 (decreasing exposure of the co-administered substrate by approximately 85%) and may be adequate prototype inhibitors to investigate intestinal DDIs mediated by OATPs.
DrugBank Data that Cites this Article
- Drugs
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Fexofenadine Solute carrier organic anion transporter family member 1A2 Protein Humans UnknownSubstrateDetails Fexofenadine Solute carrier organic anion transporter family member 2B1 Protein Humans UnknownSubstrateDetails