BACKGROUND Few studies have assessed the dose ratio of calcium gluconate to calcium chloride or defined the time course of change in serum ionized calcium concentration after intravenous injection. METHODS In a bioequivalence (dose ratio) trial, parturients undergoing cesarean delivery were randomly assigned to receive calcium chloride 0.5 grams or calcium gluconate 1.5 or 2 grams by 10-minute intravenous infusion. Venous serum ionized calcium concentration was measured prior to calcium infusion and approximately 5, 10, 15, 30, and 60 minutes after infusion start. We combined these data with serum ionized calcium concentration measurements in parturients who received 1 gram calcium chloride or saline placebo in two recent clinical trials to define the pharmacokinetics of intravenous calcium over the first hour during and after drug administration. RESULTS The bioequivalence study enrolled 34 participants, from whom we collected 181 serum ionized calcium concentration measurements. The dose ratio of calcium gluconate to calcium chloride was 3.11 (95% CI: 2.77-3.48). Population pharmacokinetics of calcium were determined using 311 serum ionized calcium concentration measurements from 70 parturients. The pharmacokinetics of intravenous calcium were described by a two-compartment model with systemic clearance of 0.18 (95% CI: 0.07-0.27) L/min, distributional clearance of 1.25 (95%CI: 1.03-1.56) L/min, central volume of 10.9 (95% CI: 9.3-12.6) L, and peripheral volume of 16.5 (95% CI: 12.5-24.7) L. After adjusting for the dose ratio, calcium gluconate and calcium chloride had identical time courses. A one-gram infusion of calcium chloride results in a peak increase in serum ionized calcium concentration of 0.39 (0.38-0.42 mmol/L), which decreases by half 29 (23-40) minutes after initiation of the 10-minute infusion. CONCLUSIONS We confirmed a 3:1 dose ratio of calcium gluconate to calcium chloride and estimated the pharmacokinetics over the first hour following intravenous delivery. These data inform clinical care and may guide future trials assessing calcium efficacy to reduce bleeding in obstetric patients. CLINICALTRIALS.GOV REGISTRATION NCT05973747 (bioequivalence), NCT05027048, and NCT03867383 (trials included in pharmacokinetic assessment).

中文翻译：

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剖宫产期间静脉注射钙的生物等效性和药代动力学。


背景 很少有研究评估葡萄糖酸钙与氯化钙的剂量比或确定静脉注射后血清离子钙浓度变化的时间进程。方法 在一项生物等效性 （剂量比） 试验中，接受剖宫产的产妇被随机分配接受氯化钙 0.5 克或葡萄糖酸钙 1.5 或 2 克，静脉输注 10 分钟。在钙输注前和输注开始后约 5 、 10 、 15 、 30 和 60 分钟测量静脉血清离子钙浓度。我们将这些数据与最近两项临床试验中接受 1 克氯化钙或生理盐水安慰剂的产妇的血清离子钙浓度测量值相结合，以确定给药期间和给药后第一个小时内静脉注射钙的药代动力学。结果 生物等效性研究招募了 34 名参与者，我们从他们那里收集了 181 次血清离子钙浓度测量。葡萄糖酸钙与氯化钙的剂量比为 3.11 （95% CI： 2.77-3.48）。使用来自 70 名产妇的 311 例血清离子钙浓度测量值确定钙的群体药代动力学。静脉补钙的药代动力学由两室模型描述，全身清除率为 0.18 （95% CI： 0.07-0.27） L/min，分布清除率为 1.25 （95% CI： 1.03-1.56） L/min，中心体积为 10.9 （95% CI： 9.3-12.6） L，外周体积为 16.5 （95% CI： 12.5-24.7） L。调整剂量比后，葡萄糖酸钙和氯化钙的时间进程相同。输注 1 克氯化钙导致血清离子钙浓度峰值增加 0.39 （0.38-0.42 mmol/L），在开始 10 分钟输注后 29 （23-40） 分钟下降一半。结论 我们确认了葡萄糖酸钙与氯化钙的剂量比为 3：1，并估计了静脉给药后 1 小时内的药代动力学。这些数据为临床护理提供了信息，并可能指导未来评估钙对减少产科患者出血的疗效的试验。CLINICALTRIALS.GOV 注册NCT05973747 （生物等效性）、NCT05027048 和 NCT03867383 （药代动力学评估中包含的试验）。