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After oral administration of 100 mg Prednimustine® to patients with metastatic breast carcinoma, prednisolone levels and the area under the plasma concentration-time curve between 2 and 24 h are approximately half of those obtained after the administration of an equivalent dose of prednisolone. As previous studies have reported up to 55% of unchanged Prednimustine in feces, it is suggested that prednisolone plasma levels are as good a parameter of Prednimustine absorption and bioavailability as chlorambucil levels, Prednimustine itself having never been detected in plasma. Whether Prednimustine is hydrolyzed in the intestine before absorption or rapidly taken up by the tissues and hydrolyzed in situ after absorption is unclear at the moment. Myelosuppressive effects of Prednimustine correlated very well with maximal prednisolone levels, emphasizing the value of prednisolone level measurements.

This study was designed to investigate the effect of continuous treatment with the anti-thyroid drug, propylthiouracil (PTU), on renal and hepatic functions in rabbits as an experimental animal model. Animals were randomly divided into four different isolated groups (n = 10); Group I received normal saline. Group II, III, and IV were daily administrated with PTU in oral dosing of 50, 75, and 150 mg/kg, BWT, respectively, for three successive weeks. Serum T 3 and T 4 levels were measured in all groups. Increased serum creatinine and blood urea nitrogen levels (P<0.05) were also associated. Moreover, liver enzymes levels, aspartate aminotransferase, alanine aminotransferase, and total serum cholesterol levels showed a significant increase in a dose and time decedent manner. Thyroid glands of PTU-treated rabbits showed variable sized-follicles lined by multiple layers of follicular cells, which displayed signs of hyperactivity as the average follicular cell height. The diameter of its width was significantly increased compared with that in the control group. Besides, follicles were filled with a variable quantity of low-dense vacuolated colloids. Kidneys of such animals showed tubulointerstitial nephritis, glomerular atrophy, and multiple focal areas of mononuclear cell reaction. While the observed hepatic lesions were in the form of severe congestion in central vein and hepatic artery, hepatocellular necrosis, and granulocytic lymphoid cellular responses around portal areas associated with peri-portal fibrosis. Such lesions were dependent on doses of PTU. This study referred to that continuous treatment with an antithyroid drug PTU induced a hypothyroid state that was associated with impaired renal and hepatic functions in rabbits. ‫ـــــــــــــــــــــــــــــــــــــــــ‬