title: On the Molecular Basis Underlying the Metabolism of Tapentadol Through Sulfation.
abstract: OBJECTIVE
  Previous studies reported that tapentadol-sulfate represented one of the major metabolites of tapentadol excreted in urine. The current study aimed to identify the human cytosolic sulfotransferases (SULTs) that is(are) capable of sulfating tapentadol and to examine whether human cells and human organ specimens are capable of sulfating tapentadol.
  
  
  METHODS
  Thirteen human SULTs, previously expressed and purified, as well as human organ cytosols, were analyzed for tapentadol-sulfating activity using an established sulfotransferase assay. Cultured HepG2 human hepatoma cells and Caco-2 human colon carcinoma cells were labeled with [35S]sulfate in the presence of different concentrations of tapentadol.
  
  
  RESULTS
  Three of the thirteen human SULTs, SULT1A1, SULT1A3, and SULT1C4, were found to display sulfating activity toward tapentadol. Kinetic analysis revealed that SULT1A3 displayed the highest catalytic efficiency in mediating the sulfation of tapentadol, followed by SULT1A1 and SULT1C4. Using cultured HepG2 and Caco-2 cells, the generation and release of sulfated tapentadol under metabolic conditions was demonstrated. Moreover, of the four human organ specimens (kidney, liver, lung, and small intestine) tested, the cytosols prepared from small intestine and liver showed significant tapentadol-sulfating capacity (at 0.0203 and 0.0054 nmol/min/mg, respectively).
  
  
  CONCLUSIONS
  Taken together, the results derived from the current study provided a molecular basis underlying the sulfation of tapentadol in humans.
authors.affiliation: Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Health Science Campus, 3000 Arlington Avenue, Toledo, OH, 43614, USA.
authors.forename: Ahsan F
authors.initials: AF
authors.lastname: Bairam
authors.affiliation: Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Health Science Campus, 3000 Arlington Avenue, Toledo, OH, 43614, USA.
authors.forename: Mohammed I
authors.initials: MI
authors.lastname: Rasool
authors.affiliation: Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Health Science Campus, 3000 Arlington Avenue, Toledo, OH, 43614, USA.|Biochemistry and Applied Biosciences, University of Miyazaki, Miyazaki, 889-2192, Japan.
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Kurogi
authors.affiliation: Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Health Science Campus, 3000 Arlington Avenue, Toledo, OH, 43614, USA. ming.liu@utoledo.edu.
authors.forename: Ming-Cheh
authors.initials: MC
authors.lastname: Liu
mesh_terms: D018938:Caco-2 Cells; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D007421:Intestine, Small / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism; D010636:Phenols / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism*; D015238:Sulfotransferases / Q000378:metabolism; D000077432:Tapentadol
chemical_list: D010636:Phenols; D013431:Sulfates; D015238:Sulfotransferases; D000077432:Tapentadol
keywords: HepG2 Cell; Human Organ; Sulfating Activity; Sulfation; Tapentadol