The Effects of Cyclophosphamide on the Pharmacokinetics of Triiodothyronine in the Male Rat

In the present study, the possibility that cyclophosphamide or a cyclophosphamide metabolite may be accelerating the clearance of triiodothyronine has been examined. Following administration of exogenous triiodothyronine to saline-and cyclophosphamide-treated rats, the area under the plasma-concentration time curve (AUC), apparent clearance (CL_app) and half-life of triiodothyronine were measured. AUC (34.43 ± 12.34 compared with 33.32 ± 9.92 nmol hL^?1), CL_app (36.30 ± 12.89 compared with 37.51 ± 11.16 mLh^?1) and half-life (7.50 ± 1.39 compared with 6.40 ± 0.96 h) were not significantly different in the control rats compared with the cyclophosphamide-treated rats. As cyclophosphamide does not appear to alter the elimination of triiodothyronine, it is likely that cyclophosphamide or a cyclophosphamide metabolite is acting at the hypothalamo-pituitary axis, reducing the synthesis or release of thyroid stimulating hormone and consequently decreasing the levels of triiodothyronine and thyroxine.