Developing a Safe Intravenous Sotalol Dosing Regimen
Developing a Safe Intravenous Sotalol Dosing Regimen
复制标题
制定安全的静脉注射索他洛尔给药方案
DOI：
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发表时间：
2010
影响因子：
4.2
通讯作者：
J. Molnar
中科院分区：
文献类型：
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作者：
J. Somberg;R. Preston;V. Ranade;J. Molnar
最近，索他洛尔的静脉注射制剂已获得美国食品药品监督管理局的批准，用于替代无法口服索他洛尔的患者的口服治疗。这项随机、2 个治疗、2 个周期的交叉研究的目的是开发一种静脉注射索他洛尔的安全给药方案，该方案提供与口服索他洛尔相似的血液浓度，因此具有相似的功效和安全性。 15 名健康受试者在 2.5 小时内接受 75 毫克静脉输注索他洛尔和 80 毫克口服索他洛尔。使用标准药代动力学方法获得最大血清浓度（Cmax）和浓度-时间曲线下面积（AUC）。在模拟研究中使用个体药代动力学参数来确定最佳的静脉给药方案。静脉注射索他洛尔超过 2.5 小时的 Cmax 显着高于口服给药（830 ± 391 vs. 601 ± 289 ng/mL，P < 0.001）。随着输注时间增加至 3、4 和 5 小时，模拟研究表明 Cmax 分别降至口服 Cmax 的 128%、113% 和 102%。输注时间的长短不影响AUC。根据这些研究，替代 80 mg 口服治疗的安全静脉注射方案需要 75 mg 静脉注射索他洛尔，5 小时输注。由于索他洛尔的药代动力学是线性且与剂量成比例的，因此在 5 小时内静脉注射 150 mg 索他洛尔将提供与 160 mg 口服索他洛尔相似的 Cmax 和 AUC。美国食品和药物管理局批准的给药方案是用 75 mg 静脉注射索他洛尔代替 80 mg 口服索他洛尔，用 150 mg 静脉注射索他洛尔代替 160 mg 口服索他洛尔，两者均给药时间超过 5 小时。
Recently, an intravenous formulation of sotalol has been approved by the food and drug administration for substitution for oral therapy in patients who are unable to take oral sotalol. The purpose of this randomized, 2-treatment, 2-period, crossover study was to develop a safe dosing regimen for intravenous sotalol that provides similar blood levels and therefore similar efficacy and safety to orally administered sotalol. Fifteen healthy subjects received 75 mg intravenous sotalol infusion administered over 2.5 hours and 80 mg oral sotalol. Standard pharmacokinetic methods were used to obtain maximum serum concentrations (Cmax) and areas under the concentration-time curves (AUC). Individual pharmacokinetic parameters were used in simulation studies to determine the optimal intravenous administration regimen. Intravenous sotalol administered over 2.5 hours resulted in a significantly greater Cmax than oral administration (830 ± 391 vs. 601 ± 289 ng/mL, P < 0.001). With increasing the length of infusions to 3, 4, and 5 hours, simulation studies showed that the Cmax decreased to 128%, 113%, and 102% of the oral Cmax. The length of infusion did not affect AUC. Based on these studies, a safe intravenous regimen for the replacement of 80-mg oral therapy requires 75 mg intravenous sotalol administered as a 5-hour infusion. Because the pharmacokinetics of sotalol are linear and dose proportional, 150 mg intravenous sotalol administered over 5 hours will provide similar Cmax and AUC as 160 mg oral sotalol. The food and drug administration-approved dosing regimen is 75 mg intravenous sotalol to replace 80 mg oral sotalol and 150 mg intravenous sotalol to replace 160 mg oral sotalol, both administered over 5 hours.