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 (CLapp) and half-life of triiodothyronine were measured. AUC (34.43 +/- 12.34 compared with 33.32 +/- 9.92 nmol h L-1). CLapp (36.30 +/- 12.89 compared with 37.51 +/- 11.16 mL h-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.