Riddell J G, Neill J D, Kelly J G, McDevitt D G
Clin Pharmacol Ther. 1980 Nov;28(5):565-74. doi: 10.1038/clpt.1980.204.
Propranolol kinetics was studied in six hyperthyroid and six hypothyroid patients who received single oral and intravenous doses of propranolol when they had thyroid dysfunction and again when they had become euthyroid. Change in thyroid status from hyperthyroid to euthyroid produced no change in the elimination half-life (t 1/2) of oral propranolol (3.2 +/- 0.5 to 4.1 +/- 0.7 hr), the oral clearance (38.4 +/- 7.3 to 27.4 +/- 2.4 ml/min/kg), the elimination t 1/2 of intravenous propranolol (2.5 +/- 0.3 to 3.5 +/- 0.7 hr), and the apparent volume of distribution (4.8 +/- 0.4 to 3.8 +/- 0.5 l/kg). The systemic clearance of propranolol, however, was greater when the patients were hyperthyroid (20.8 +/- 2.5 ml/min/kg) than when they had become euthyroid (11.7 +/- 1.7 ml/min/kg). The elimination t 1/2 after oral propranolol was longer in the hypothyroid (3.7 +/- 0.5 hr) than in the euthyroid state (2.0 +/- 0.1 hr). No other changes were observed in the kinetic parameters measured when these hypothyroid patients had become euthyroid. Adequate beta-adrenoceptor blockade in hyperthyroid patients may require higher propranolol dosage than expected.
在六名甲状腺功能亢进和六名甲状腺功能减退患者中研究了普萘洛尔的动力学，这些患者在甲状腺功能异常时接受了单次口服和静脉注射普萘洛尔，在甲状腺功能恢复正常后再次接受给药。甲状腺状态从甲状腺功能亢进转变为甲状腺功能正常后，口服普萘洛尔的消除半衰期（t1/2）（从3.2±0.5小时变为4.1±0.7小时）、口服清除率（从38.4±7.3毫升/分钟/千克变为27.4±2.4毫升/分钟/千克）、静脉注射普萘洛尔的消除t1/2（从2.5±0.3小时变为3.5±0.7小时）以及表观分布容积（从4.8±0.4升/千克变为3.8±0.5升/千克）均未发生变化。然而，患者甲状腺功能亢进时普萘洛尔的全身清除率（20.8±2.5毫升/分钟/千克）高于甲状腺功能恢复正常时（11.7±1.7毫升/分钟/千克）。甲状腺功能减退患者口服普萘洛尔后的消除t1/2（3.7±0.5小时）比甲状腺功能正常状态时（2.0±0.1小时）更长。当这些甲状腺功能减退患者甲状腺功能恢复正常时，所测量的动力学参数未观察到其他变化。甲状腺功能亢进患者可能需要比预期更高剂量的普萘洛尔才能实现充分的β-肾上腺素能受体阻滞。
