61 PROPYLTHIOURACIL AND METHIMAZOLE PHARMACOLOGY IN CHILDREN AND ADOLESCENTS WITH GRAVES DISEASE

Concentrations of propylthiouracil (PTU) and methimazole (MMI) in plasma and thyroid glands were measured. A single oral dose of the drugs (100 to 280 mg/m2 of PTU or 20 mg/m2 of MMI) induced a rapid increase of plasma levels reaching a peak within 1 hr for both PTU and MMI. Peak PTU values ranged from 7.2 to 18 μg/m1 with the administered dose. Its mean plasma half-life was 1.36 hrs, and its mean distribution volume was 326 ml/kg. Plasma levels of MMI showed a mean peak value of 1.03 μg/ml, a mean half-life of 4.56 hrs, and a mean distribution volume of 630 ml/kg. Intrathyroidal concentrations of PTU were measured in needle biopsy specimens and were 2.06 - 4.31 μg/g, 4.56 - 17.8 μg/g and 1.09 - 4.48 μg/g at 2, 12 and 24 hrs after 200 mg/m2 of MMI respectively. Intrathyroidal MMI was measured in surgically obtained specimens and was 1.1- 1.3 μg/g and 0.78 - 1.40 μg/g at 5 and 18 hrs after 10 - 20 mg/m2 of MMI respectively. These values far exceeded the plasma values at the respective times except for 2 hrs after PTU. Our results indicate: 1) elimination of PTU and MMI from the thyroid gland is much slower than from plasma, and 2) a single daily dose of PTU or MMI is adequate for the treatment of Graves disease.