Edward C. Gomez

Efficacy of mycophenolic acid for the treatment of psoriasis

The efficacy of orally administered mycophenolic acid (MPA), an inhibitor of guanosine monophosphate (GMP) synthesis, for the treatment of psoriasis, was studied in a double-blind fashion. Of twenty-one patients completing the study period, ten of eleven patients treated with MPA had a greater than 25% decrease in severity score compared with only two of ten patients treated with placebo. The placebo group had a slight increase in severity score compared to almost 50% reduction in the average severity score of the MPA-treated group. After termination of the double-blind portion of the study, the placebo group was treated with MPA and showed a 60% decrease in severity score. Adverse effects encountered included anorexia, nausea, vomiting, and diarrhea. One patient had an uncomplicated episode of herpes zoster. Other than a mild decrease hemoglobin, no hematologic toxicity was noted.

Cutaneous β‐glucuronidase: cleavage of mycophenolic acid by preparations of mouse skin

Mycophenolic acid, a new chemotherapeutic agent for the treatment of psoriasis, is known to be rapidly conjugated on absorption and to circulate largely in the form of its glucuronide conjugate. Since this metabolite does not readily penetrate intact cells and is cleaved by the enzyme β‐glucuronidase to yield free mycophenolic acid, the ability of preparations of mouse skin to cleave mycophenolic glucuronide was studied. The time course of mycophenolic acid liberation by such preparations and the dependence upon the amount of enzyme preparation were demonstrated. Preparations of mouse skin and mouse liver, kidney, spleen, lung, heart and small intestine were assayed for β‐glucuronidase activity using ρ‐nitrophenyl‐β‐D‐glucuronide as substrate. Skin yielded preparations with higher β‐glucuronidase activity per/mg protein than any of the other organs tested. When expressed on the basis of β‐glucuronidase activity recovered per milligram of tissue DNA, skin, liver and kidney showed higher levels than the other organs tested.