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.
Angley
M T
MT
School of Pharmacy and Medical Sciences, University of South Australia, Adelaide.
Sansom
L N
LN
Smeaton
T C
TC
Stupans
I
I
D000477:Alkylating Agents / Q000494:pharmacology*; D000818:Animals; D003520:Cyclophosphamide / Q000494:pharmacology*; D006207:Half-Life; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014284:Triiodothyronine / Q000493:pharmacokinetics*
D000477:Alkylating Agents; D014284:Triiodothyronine; D003520:Cyclophosphamide