Drug General Information (ID: DDIRJVYQBG)
  Drug Name Testosterone Drug Info Pazopanib Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antiandrogens Vegf/Vegfr Inhibitors
  Structure

 Mechanism of Testosterone-Pazopanib Interaction (Severity Level: Major)
     Transporter inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Testosterone Pazopanib
      Mechanism P-gp inhibitor P-gp substrate
      Key Mechanism Factor 1
Factor Name P-glycoprotein 1
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Structure Sequence
MDLEGDRNGGAKKKNFFKLNNKSEKDKKEKKPTVSVFSMFRYSNWLDKLYMVVGTLAAIIHGAGLPLMMLVFGEMTDIFANAGNLEDLMSNITNRSDINDTGFFMNLEEDMTRYAYYYSGIGAGVLVAAYIQVSFWCLAAGRQIHKIRKQFFHAIMRQEIGWFDVHDVGELNTRLTDDVSKINEGIGDKIGMFFQSMATFFTGFIVGFTRGWKLTLVILAISPVLGLSAAVWAKILSSFTDKELLAYAKAGAVAEEVLAAIRTVIAFGGQKKELERYNKNLEEAKRIGIKKAITANISIGAAFLLIYASYALAFWYGTTLVLSGEYSIGQVLTVFFSVLIGAFSVGQASPSIEAFANARGAAYEIFKIIDNKPSIDSYSKSGHKPDNIKGNLEFRNVHFSYPSRKEVKILKGLNLKVQSGQTVALVGNSGCGKSTTVQLMQRLYDPTEGMVSVDGQDIRTINVRFLREIIGVVSQEPVLFATTIAENIRYGRENVTMDEIEKAVKEANAYDFIMKLPHKFDTLVGERGAQLSGGQKQRIAIARALVRNPKILLLDEATSALDTESEAVVQVALDKARKGRTTIVIAHRLSTVRNADVIAGFDDGVIVEKGNHDELMKEKGIYFKLVTMQTAGNEVELENAADESKSEIDALEMSSNDSRSSLIRKRSTRRSVRGSQAQDRKLSTKEALDESIPPVSFWRIMKLNLTEWPYFVVGVFCAIINGGLQPAFAIIFSKIIGVFTRIDDPETKRQNSNLFSLLFLALGIISFITFFLQGFTFGKAGEILTKRLRYMVFRSMLRQDVSWFDDPKNTTGALTTRLANDAAQVKGAIGSRLAVITQNIANLGTGIIISFIYGWQLTLLLLAIVPIIAIAGVVEMKMLSGQALKDKKELEGSGKIATEAIENFRTVVSLTQEQKFEHMYAQSLQVPYRNSLRKAHIFGITFSFTQAMMYFSYAGCFRFGAYLVAHKLMSFEDVLLVFSAVVFGAMAVGQVSSFAPDYAKAKISAAHIIMIIEKTPLIDSYSTEGLMPNTLEGNVTFGEVVFNYPTRPDIPVLQGLSLEVKKGQTLALVGSSGCGKSTVVQLLERFYDPLAGKVLLDGKEIKRLNVQWLRAHLGIVSQEPILFDCSIAENIAYGDNSRVVSQEEIVRAAKEANIHAFIESLPNKYSTKVGDKGTQLSGGQKQRIAIARALVRQPHILLLDEATSALDTESEKVVQEALDKAREGRTCIVIAHRLSTIQNADLIVVFQNGRVKEHGTHQQLLAQKGIYFSMVSVQAGTKRQ
Gene Name ABCB1
Uniprot ID MDR1_HUMAN
KEGG Pathway hsa:5243
Protein Family ABC transporter superfamily
Protein Function
Translocates drugs and phospholipids across the membrane (PubMed:8898203, PubMed:2897240, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:9038218).
    Click to Show/Hide
      Mechanism Description
  • Decreased clearance of Pazopanib due to the transporter inhibition by Testosterone 

Recommended Action
      Management Concomitant use of pazopanib with potent inhibitors of P-gp or BCRP should generally be avoided. Selection of an alternate concomitant medication with no or minimal potential to inhibit P-gp or BCRP should be considered. Patients should have liver function tests (ALT, AST, bilirubin), electrocardiograms, and serum electrolyte levels performed at baseline and regular intervals as recommended in the product labeling. Patients should be advised to notify their physician if they experience signs and symptoms of hepatotoxicity such as fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice. In addition, they should seek medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, palpitations, or syncope.

References
1 Cerner Multum, Inc. "Australian Product Information.".
2 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
3 Product Information. Votrient (pazopanib). GlaxoSmithKline, Research Triangle Park, NC.
4 Tan AR, Gibbon DG, Stein MN, et al. "Effects of ketoconazole and esomeprazole on the pharmacokinetics of pazopanib in patients with solid tumors." Cancer Chemother Pharmacol 71 (2013): 1635-43. [PMID: 23636448]