[Effects of different thyroid status on the pharmacokinetics of diazepam].
Experimental models of hypothyroidism and hyperthyroidism in Sprague-Dawley rats were established in this study. Diazepam was given to rats at a single oral dose of 30-40 mg.kg-1 and the plasma concentration of diazepam was detected by HPLC. The results showed that the plasma concentration of diazepam was significantly higher in hypothyroid rats than that in controls (P < 0.05). The Cmax, AUC and T1/2 (Ka) were increased. The Vd was decreased and the elimination was slowed. Mild hyperthyroidism showed nearly no effect on the plasma concentration, Cmax and AUC of diazepam in the rats. But when the rats became more heavily hyperthyroid, the plasma concentration, Cmax and AUC of diazepam were increased gradually. The absorption of diazepam was changed slightly in mild and moderate hyperthyroid rats, the Vd was decreased and the elimination was accelerated. In heavily hyperthyroid rats, however, the absorption of diazepam was obviously accelerated. The Vd was decreased and the elimination was slowed. Therefore, we conclude that different thyroid status may have different effects on the pharmacokinetics of diazepam.
Xu
F
F
Department of Pharmacology, Beijing Medical University, Beijing 100083.
Zhang
Y
Y
Lou
Y
Y
D000818:Animals; D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D003975:Diazepam / Q000493:pharmacokinetics*; D006980:Hyperthyroidism / Q000378:metabolism*; D007037:Hypothyroidism / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D008713:Methimazole; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D014151:Anti-Anxiety Agents; D008713:Methimazole; D003975:Diazepam