Format

Send to

Choose Destination
J Pharm Sci. 2017 Sep;106(9):2312-2325. doi: 10.1016/j.xphs.2017.04.004. Epub 2017 Apr 13.

Intestinal Drug Interactions Mediated by OATPs: A Systematic Review of Preclinical and Clinical Findings.

Author information

1
School of Pharmacy, University of Washington, Seattle, Washington 98195.
2
Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, California 95211.
3
School of Pharmacy, University of Washington, Seattle, Washington 98195. Electronic address: imaj@uw.edu.

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 ∼85%) and may be adequate prototype inhibitors to investigate intestinal DDIs mediated by OATPs.

KEYWORDS:

drug interaction; inhibition; intestinal absorption; organic anion-transporting polypeptide transporters; polymorphism; transporter

PMID:
28414144
DOI:
10.1016/j.xphs.2017.04.004
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center