@article {548, title = {Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5{\textquoteright}-diphospho-glucuronosyltransferase isoforms}, journal = {Pharmacognosy Research}, volume = {7}, year = {2015}, month = {October 2015}, pages = {341-349}, type = {Original Article}, chapter = {341}, abstract = {

Background: Glucuronidation catalyzed by uridine 5{\textquoteright}-diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation. Objectives: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms. Materials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection. Results: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 {\textpm} 1.51 μM followed by buprenorphine with an IC50 value of 73.22 {\textpm} 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 {\textpm} 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 {\textpm} 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 {\textpm} 1.30, 26.44 {\textpm} 1.31, and 27.28 {\textpm} 1.18 μM. Conclusion: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are

}, keywords = {4-methylumbelliferone, 7-hydroxymitragynine, Buprenorphine, Glucuronidation, Ketamine, Mitragynine.}, doi = {10.4103/0974-8490.159580}, author = {Munirah Haron and Sabariah Ismail} }