INT95102

Context Info Confidence 0.75 First Reported 2001 Last Reported 2008 Negated 0 Speculated 0 Reported most in Abstract Documents 3 Total Number 5 Disease Relevance 0.69 Pain Relevance 4.24

transmembrane transporter activity (SLC22A8) plasma membrane (SLC22A8) transmembrane transport (SLC22A8)

Anatomy Link Frequency urine 2 renal proximal tubules 1 SLC22A8 (Homo sapiens)

Pain Link Frequency Relevance Heat cINOD 43 99.90 methotrexate 51 99.58 Bile 1 98.24 Paracetamol 6 84.80 aspirin 3 70.40

Disease Link Frequency Relevance Heat INFLAMMATION 8 96.94 Disease 1 79.60

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Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Coadministration of methotrexate and nonsteroidal anti-inflammatory drugs (NSAIDs) can cause a pharmacokinetic interaction and a subsequent increase in blood methotrexate concentrations. methotrexate and most NSAIDs are excreted into urine via organic anion transporter 3 (OAT3).

Localization (excreted) of OAT3 in urine associated with inflammation, cinod and methotrexate

1) Confidence 0.75 Published 2008 Journal Eur. J. Pharmacol. Section Abstract Doc Link 18789319 Disease Relevance 0.17 Pain Relevance 1.12

In conclusion, methotrexate and most NSAIDs are substrates of hOAT3, and those drugs compete via hOAT3 in tubular secretion, the major mechanism of the interaction between methotrexate and NSAIDs.

Localization (secretion) of hOAT3 associated with cinod and methotrexate

2) Confidence 0.70 Published 2008 Journal Eur. J. Pharmacol. Section Abstract Doc Link 18789319 Disease Relevance 0.07 Pain Relevance 1.35

Coadministration of methotrexate and nonsteroidal anti-inflammatory drugs (NSAIDs) can cause a pharmacokinetic interaction and a subsequent increase in blood methotrexate concentrations. methotrexate and most NSAIDs are excreted into urine via organic anion transporter 3 (OAT3).

Localization (excreted) of organic anion transporter 3 in urine associated with inflammation, cinod and methotrexate

3) Confidence 0.65 Published 2008 Journal Eur. J. Pharmacol. Section Abstract Doc Link 18789319 Disease Relevance 0.17 Pain Relevance 1.11

The hOAT3 protein was shown to be localized in the basolateral membrane of renal proximal tubules and the hOAT3 gene was determined to be located on the human chromosome 11q12-q13.3 by fluorescent in situ hybridization analysis.

Localization (localized) of hOAT3 in renal proximal tubules

4) Confidence 0.64 Published 2001 Journal Mol. Pharmacol. Section Abstract Doc Link 11306713 Disease Relevance 0.10 Pain Relevance 0.18

Human organic anion transporters hOAT1 (SLC22A6) and hOAT3 (SLC22A8) are responsible for renal tubular secretion of an antifolic acid methotrexate, and are considered to be involved in drug interaction of methotrexate with nonsteroidal anti-inflammatory drugs (NSAIDs).

Localization (secretion) of hOAT3 associated with inflammation, cinod and methotrexate

5) Confidence 0.62 Published 2004 Journal Drug Metab. Pharmacokinet. Section Abstract Doc Link 15548848 Disease Relevance 0.17 Pain Relevance 0.47

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