Bioequivalence and pharmacokinetics of intravenous calcium during cesarean delivery.

IF 9.1 1区医学 Q1 ANESTHESIOLOGY Anesthesiology Pub Date : 2024-10-03 DOI:10.1097/ALN.0000000000005248

Jessica R Ansari, Daniel J Conti, Guillermina Michel, Alla Yarmosh, Naida M Cole, Steven L Shafer

{"title":"Bioequivalence and pharmacokinetics of intravenous calcium during cesarean delivery.","authors":"Jessica R Ansari, Daniel J Conti, Guillermina Michel, Alla Yarmosh, Naida M Cole, Steven L Shafer","doi":"10.1097/ALN.0000000000005248","DOIUrl":null,"url":null,"abstract":"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).","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":" ","pages":""},"PeriodicalIF":9.1000,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Anesthesiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/ALN.0000000000005248","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ANESTHESIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

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).

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

剖宫产期间静脉注射钙剂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和氯化钙的剂量比，也很少有研究定义静脉注射后血清离子钙浓度变化的时间过程：很少有研究对葡萄糖酸钙与氯化钙的剂量比进行评估，也很少有研究对静脉注射后血清离子钙浓度变化的时间过程进行定义：在一项生物等效性（剂量比）试验中，剖宫产产妇被随机分配接受氯化钙 0.5 克或葡萄糖酸钙 1.5 克或 2 克，静脉注射时间为 10 分钟。在输注钙剂前以及输注开始后约 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结果相结合，以确定给药期间和给药后一小时内静脉注射钙的药代动力学：生物等效性研究共有 34 人参加，我们收集了 181 次血清离子钙浓度测量结果。葡萄糖酸钙与氯化钙的剂量比为 3.11（95% CI：2.77-3.48）。通过对 70 名产妇的 311 次血清离子钙浓度测量，确定了钙的群体药代动力学。静脉注射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) 升/分钟，分布清除率为 1.25 (95%CI: 1.03-1.56) 升/分钟，中心容量为 10.9 (95% CI: 9.3-12.6) 升，外周容量为 16.5 (95% CI: 12.5-24.7) 升。输注一克氯化钙可使血清离子钙浓度达到 0.39（0.38-0.42 mmol/L）的峰值，在开始输注 10 分钟后的 29（23-40）分钟内，血清离子钙浓度下降一半：我们确认葡萄糖酸钙和氯化钙的剂量比为 3:1，并估算了静脉注射后一小时内的药代动力学。这些数据为临床护理提供了参考，并可指导未来评估钙对减少产科病人出血疗效的试验：NCT05973747（生物等效性）、NCT05027048 和 NCT03867383（纳入药代动力学评估的试验）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Anesthesiology 医学-麻醉学

CiteScore

10.40

自引率

5.70%

发文量

542

审稿时长

3-6 weeks

期刊介绍： With its establishment in 1940, Anesthesiology has emerged as a prominent leader in the field of anesthesiology, encompassing perioperative, critical care, and pain medicine. As the esteemed journal of the American Society of Anesthesiologists, Anesthesiology operates independently with full editorial freedom. Its distinguished Editorial Board, comprising renowned professionals from across the globe, drives the advancement of the specialty by presenting innovative research through immediate open access to select articles and granting free access to all published articles after a six-month period. Furthermore, Anesthesiology actively promotes groundbreaking studies through an influential press release program. The journal's unwavering commitment lies in the dissemination of exemplary work that enhances clinical practice and revolutionizes the practice of medicine within our discipline.