Table 1

Summary of female liver donor demographics and EM-652 glucuronidation activity.

DonorAgeSmokerAlcohol ConsumptionMedicineGlucuronide formationRatio EM-652-7-G/ EM-652-4′-G
EM-652-4′-GEM-652-7-G
pmol/min/mg of protein
Pool (n = 5)N.D.N.D.N.D.N.D.15.6  ± 0.353.0  ± 2.23.4
Patient 159NoYesNifedipine15.8  ± 0.348.4  ± 1.53
Diabetes
Patient 265YesNoGlibenclamide, warfarin36.0  ± 2.3134.9  ± 5.43.7
Diabetes
Patient 352YesNoInsulin, Paroxetine, Buspirone11.5  ± 1.541.6  ± 4.93.6
Diabetes
Patient 444YesNoInsulin, sumatriptan succinate, isometheptine mucate/ dichlovalphenazome/acetaminophen, Sulax9.9  ± 0.142.6  ± 1.24.3
Patient 542NoNoClodine20.9  ± 0.586.9  ± 1.14.2
Patient 649NoNoConjugated estrogen, Oxybutynin, Trazodone19.6  ± 1.091.8  ± 5.14.7
Anorexia
Patient 734YesNoLanotil, Diazepam36.9  ± 1.6154.9  ± 4.94.2
Patient 853NoNoEstrogen25.7  ± 1.5100.2  ± 6.53.9

The level of EM-652 glucurono-conjugation by female liver was determined for each hydroxyl position of the molecule by incubating microsomal proteins of liver samples (40 mg) and EM-652 (500 mM) for 3 h in presence of UDP-glucuronic acid (2 mM). EM-652-4′-glucuronide (EM-652-4′-G) and EM-652-7-glucuronide (EM-652-7-G) formation was detected and quantified using LC/MS-MS analysis. Values represent the mean of two independent esxperiments ± S.D.

    • N.D., not determined.