Müller P B, Wolfsheimer K J, Taboada J, Hosgood G, Partington B P, Gaschen F P
Department of Veterinary Physiology, Pharmacology and Toxicology, School of Veterinary Medicine, Louisiana State University, Baton Rouge 70803, USA.
J Vet Intern Med. 2000 Mar-Apr;14(2):157-64. doi: 10.1892/0891-6640(2000)014<0157:eolpto>2.3.co;2.
Phenobarbital can interfere with the thyroid axis in human beings and rats by accelerating hepatic thyroxine metabolism because of enzyme induction. In human beings, it also can interfere with the low-dose dexamethasone suppression test (LDDST) used to assess adrenal function by accelerating dexamethasone metabolism. This effect can cause a lack of suppression of pituitary ACTH and subsequent adrenal cortisol release after dexamethasone administration. The effects of phenobarbital on the thyroid axis, the adrenal axis, and adrenal function tests were prospectively investigated in 12 normal, adult dogs. Phenobarbital was administered at 5 mg per kilogram of body weight (range, 4.8-6.6 mg/kg) PO q12h for 29 weeks, resulting in therapeutic serum concentrations (20-40 microg/mL). Serum total thyroxine (TT4), free thyroxine (FT4) by equilibrium dialysis, total triiodothyronine (TT3), thyrotropin (TSH), and cholesterol were determined before and during phenobarbital treatment. LDDST, ACTH stimulation tests, and ultrasonographic evaluation of the adrenal glands were performed before and during treatment. TT4 and FT4 decreased significantly (P < or = .05), TT3 had minimal fluctuation, TSH had only a delayed compensatory increase, and cholesterol increased during phenobarbital treatment. The delayed increase in TSH, despite persistent hypothyroxinemia, suggests that accelerated hepatic thyroxine elimination may not be the only effect of phenobarbital on the thyroid axis. There was no significant effect of phenobarbital on either of the adrenal function tests. With the methods employed, we did not find any effects of the drug on the hormonal equilibrium of the adrenal axis.
苯巴比妥可通过酶诱导加速肝脏甲状腺素代谢，从而干扰人类和大鼠的甲状腺轴。在人类中，它还可通过加速地塞米松代谢来干扰用于评估肾上腺功能的低剂量地塞米松抑制试验（LDDST）。这种效应可导致地塞米松给药后垂体促肾上腺皮质激素（ACTH）缺乏抑制以及随后肾上腺皮质醇释放。对12只正常成年犬前瞻性研究了苯巴比妥对甲状腺轴、肾上腺轴及肾上腺功能试验的影响。苯巴比妥按每千克体重5毫克（范围为4.8 - 6.6毫克/千克）口服，每12小时一次，共给药29周，从而产生治疗性血清浓度（20 - 40微克/毫升）。在苯巴比妥治疗前及治疗期间测定血清总甲状腺素（TT4）、平衡透析法测定的游离甲状腺素（FT4）、总三碘甲状腺原氨酸（TT3）、促甲状腺激素（TSH）及胆固醇。在治疗前及治疗期间进行LDDST、ACTH刺激试验及肾上腺超声检查。在苯巴比妥治疗期间，TT4和FT4显著降低（P≤0.05），TT3波动极小，TSH仅有延迟的代偿性升高，胆固醇升高。尽管持续存在甲状腺素血症，但TSH延迟升高表明肝脏甲状腺素消除加速可能不是苯巴比妥对甲状腺轴的唯一作用。苯巴比妥对任何一项肾上腺功能试验均无显著影响。采用这些方法，我们未发现该药物对肾上腺轴激素平衡有任何影响。
