https://orcid.org/0000-0003-1142-8339
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.
In a bioequivalence (dose ratio) trial, parturients undergoing cesarean delivery were randomly assigned to receive calcium chloride (0.5 g) or calcium gluconate (1.5 or 2 g) by 10-min intravenous infusion. Venous serum ionized calcium concentration was measured before calcium infusion and approximately 5, 10, 15, 30, and 60 min after infusion start. These data were combined with serum ionized calcium concentration measurements in parturients who received 1 g 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.
The bioequivalence study enrolled 34 participants, from whom were collected 181 serum ionized calcium concentration measurements. The dose ratio of calcium gluconate to calcium chloride was 3.11 (95% CI, 2.77 to 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 to 0.27) l/min, distributional clearance of 1.25 (95% CI, 1.03 to 1.56) l/min, central volume of 10.9 (95% CI, 9.3 to 12.6) l, and peripheral volume of 16.5 (95% CI, 12.5 to 24.7) l. After adjusting for the dose ratio, calcium gluconate and calcium chloride had identical time courses. A 1-g infusion of calcium chloride resulted in a peak increase in serum ionized calcium concentration of 0.39 (0.38 to 0.42 mM), which decreased by half (29 [23 to 40] min) after initiation of the 10-min infusion.
This study confirmed a 3:1 dose ratio of calcium gluconate to calcium chloride and estimated the pharmacokinetics over the first hour after intravenous delivery. These data inform clinical care and may guide future trials assessing calcium efficacy to reduce bleeding in obstetric patients.
Anesthesiologists frequently administer calcium chloride or calcium gluconate intravenously to patients for a variety of approved as well as off-label indications
Misunderstanding of the relative bioequivalence (dose ratio) of calcium gluconate to calcium chloride may lead to incorrect dosing and adverse patient outcomes
A bioequivalence (dose ratio) study of calcium gluconate and calcium chloride was conducted in parturients randomly assigned to receive intravenous infusions of one or the other after umbilical cord clamping
A 3-g dose of intravenously administered calcium gluconate was bioequivalent to a 1-g dose of calcium chloride
A population pharmacokinetic analysis was also conducted; the peak increase in serum ionized calcium concentrations after a 10-min intravenous infusion of 1 g calcium chloride or 3 g calcium gluconate was 0.4 mM
The increase in serum ionized calcium concentration 30 min after beginning the calcium infusion was half of the peak increase
