McDewitt D G, Shanks R G
Br J Clin Pharmacol. 1977 Apr;4(2):153-6. doi: 10.1111/j.1365-2125.1977.tb00687.x.
Sotalol 400 mg orally was given to five healthy male volunteers as a single dose and then subsequently once daily for 8 days. Following the single dose and again after the eighth daily dose, blood samples were obtained at 3, 7, 12, 24, 36 and 48 h for plasma sotalol estimation. During the 8-day course of sotalol 400 mg once daily, the effect was assessed by exercise testing and blood samples drawn for plasma sotalol measurement at 0 and 3 h with each dose. The elimination half-life after chronic administration (17.7 ± 2.6 h) was not significantly different from that obtained after the single dose (15.5 ± 1.2 h). No difference occurred either in the comparable plasma concentrations on both elimination curves. It would appear, therefore, that chronic administration of sotalol does not alter its kinetics. Drug accumulation, measured as AUC / AUC, showed a mean value of 0.95 ± 0.18, indicating that accumulation had not occurred. Mean reduction of exercise heart rate ranged from a minimum of 20.5 ± 2.0% at time 0 on Day 8 to a maximum of 38.7 ± 1.1% at +3 h on Day 4. The minimum blockade in any individual during the 8 days was 14.5%. There was a significant correlation between percentage reduction in exercise heart rate and plasma sotalol concentration. Once daily administration of sotalol 400 mg orally would, therefore, appear to be an effective therapeutic regimen when sustained β-adrenoceptor blockade is required.
对5名健康男性志愿者口服给予400毫克索他洛尔单剂量，随后每天一次，共8天。在给予单剂量后以及第8次每日剂量后，分别于3、7、12、24、36和48小时采集血样，以测定血浆索他洛尔浓度。在每日一次给予400毫克索他洛尔的8天疗程中，通过运动试验评估其效果，并在每次给药后的0小时和3小时采集血样以测定血浆索他洛尔浓度。慢性给药后的消除半衰期（17.7±2.6小时）与单剂量给药后的消除半衰期（15.5±1.2小时）无显著差异。两条消除曲线上的可比血浆浓度也无差异。因此，似乎索他洛尔的慢性给药不会改变其动力学。以AUC/AUC衡量的药物蓄积显示平均值为0.95±0.18，表明未发生蓄积。运动心率的平均降低幅度从第8天0小时的最低20.5±2.0%到第4天+3小时的最高38.7±1.1%不等。在这8天中，任何个体的最低阻断率为14.5%。运动心率降低百分比与血浆索他洛尔浓度之间存在显著相关性。因此，当需要持续的β-肾上腺素能受体阻断时，每日一次口服400毫克索他洛尔似乎是一种有效的治疗方案。
