A possible mechanism for the decrease in serum thyroxine level by phenobarbital in rodents.

Effects of phenobarbital (PB) on the levels of serum thyroid hormones such as total thyroxine (T(4)) and triiodothyronine were examined in male mice, hamsters, rats, and guinea pigs. One day after the final administration of PB (80 mg/kg, intraperitoneal, once daily for 4 days), significant decreases in the levels of the serum total T(4) and free T(4) occurred in mice, hamsters, and rats, while a significant decrease in the level of serum triiodothyronine was observed in hamsters and rats among the animals examined. In addition, a significant decrease in the level of serum thyroid-stimulating hormone was observed in only hamsters among the rodents examined. Significant increases in the level and activity of hepatic T(4)-UDP-glucuronosyltransferase (UGT1A) after the PB administration occurred in mice, hamsters, and rats, while the increase in the amount of biliary [(125)I]T(4)-glucuronide after an intravenous injection of [(125)I]T(4) to the PB-pretreated animals occurred only in rats. In mice, rats, and hamsters, but not guinea pigs, PB pretreatment promoted the clearance of [(125)I]T(4) from the serum, led to a significant increase in the steady-state distribution volumes of [(125)I]T(4), and raised the concentration ratio (Kp value) of the liver to serum and the liver distribution of [(125)I]T(4). The present findings indicate that the PB-mediated decreases in the serum T(4) level in mice, hamsters, and rats, but not guinea pigs, occur mainly through an increase in the accumulation level of T(4) in the liver.