Methods for treating testosterone deficiency in men and methods for precise dosing of UGT2B17 substrate drugs
Treatment of testosterone deficiency in men by a precision medicine approach using a biomarker of activity of UGT2B17 that is involved in testosterone urinary elimination. By inhibiting UGT2B17, alone or in combination with administration of testosterone, testosterone deficiency in men can be treatable. Further, a method of dose selection for precise dosing of UGT2B17 substrate drugs is provided. Additionally, methods for safe dosing of pharmaceutical agents that undergo UGT2B17-mediated acyl glucuronidation are provided.
1. A method for treating a subject with a pharmaceutical agent that is at least partially metabolized by UGT2B17-dependent glucuronidation, comprising the steps of:
determining the activity of UGT2B17 according to the presence of one or more endogenous biomarkers of UGT2B17 activity in a sample obtained from the subject, wherein the one or more biomarkers of UGT2B17 activity is a ratio of a concentration of testosterone glucuronide (TG) to a concentration of aldosterone glucuronide (AG) in the sample;
identifying an effective therapeutic amount of a pharmaceutical agent, wherein at least a portion of the pharmaceutical agent is metabolized by UGT2B17-dependent glucuronidation, by adjusting the portion of the agent metabolized by UGT2B17 proportionally to the UGT2B17 activity; and
administering the effective therapeutic amount of the pharmaceutical agent to the subject in need thereof.
2. The method of claim 1 , wherein the pharmaceutical agent is vorinostat, exemestane, or clopidogrel.
3. The method of claim 1 , wherein the sample is blood, urine, plasma, or serum.
4. The method of claim 1 , wherein the determining the presence of one or more endogenous biomarkers of UGT2B17 activity in the sample is done by LC/MS.
5. The method of claim 1 , wherein the effective therapeutic amount is an amount that does not result in hepatotoxicity caused by UGT2B17 mediated glucuronidation in the subject.