Reaction products of sodium glucoheptonate with copper sulfate and ammonium hydroxide

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable well-documented publication which meets basic scientific principles.

Data source

Reference

Reference Type:

publication

Title:

Comparative Effects of Calcium Chloride and Calcium Gluceptate

Author:

Drop, L.J., Cullen, D.J.

Year:

1980

Bibliographic source:

Br.J. Anaesth. (1980), 52, 501.

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Effects of CaCl2 and Ca gluceptate injections on haemodynamic variables and on plasma ionized calcium concentrations were studied in ten patients following abdominal or vascular surgery.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Calcium glucoheptonate

EC Number:

241-203-6

EC Name:

Calcium glucoheptonate

Cas Number:

17140-60-2

Molecular formula:

C7H14O8.1/2Ca

IUPAC Name:

calcium bis(2,3,4,5,6,7-hexahydroxyheptanoate) (non-preferred name)

Test material form:

other: injections

Details on test material:

Name of test material (as cited in study report): Calcium gluceptate
- Molecular formula (if other than submission substance): C14H26CaO16•xH2O
- Molecular weight (if other than submission substance): 490.43 (anhydrous basis)
- Smiles notation (if other than submission substance): C(C(C(C(C(C(C(=O)[O-])O)O)O)O)O)O.C(C(C(C(C(C(C(=O)[O-])O)O)O)O)O)O.[Ca+2] (anhydrous basis)

Test animals

Species:

other: human

Sex:

male/female

Administration / exposure

Route of administration:

intravenous

Vehicle:

not specified

Details on exposure:

Ten patients who required artificial ventilation of the lungs following major abdominal or vascular surgery were studied. The age range was 27-90 yr body weight 48.6-76.9 kg. In each patient, surgery had been completed at least 12 h before the time of study; no blood or blood products had been administered in the preceding 4-h period. During the study period, i.v. fluids were restricted to 25 mL/h. Haemodynamic variables (mean arterial pressure (MAP), mean right atrial pressure (RAP) and heart rate (HR)) were monitored immediately before the calcium infusion and 5, 10, 20 and 30 min following completion of the calcium infusion. Plasma ionized calcium concentration were measured as well.

Doses:

20 mL containing 18 mg elemental Ca /mL injection during 5 min.

Statistics:

Student's t test was used to test for statistical significance; values are given as mean± SEM.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

other: effective dose

Effect level:

18 other: mg elemental Ca /mL injection of Ca glucoheptonate

Based on:

element

Remarks:

Calcium

Remarks on result:

other: Calcium infusion resulted in a sustained increase in [Ca2+] plasma levels and in mean arterial pressure. No significant changes were recorded in mean right atrial pressure, heart rate or cardiac rhythm.

Any other information on results incl. tables

"Details of the patients are in table I. Mean initial [Ca2+] before each calcium infusion was less than normal (1.12 + 0.03 mmol litre-1) (Drop et al., 1978) and less than predicted by the McLean-Hastings nomogram (McLean and Hastings, 1935) (fig. 1). Calcium infusion resulted in a sustained increase in [Ca2+] (table II) and in mean arterial pressure (table III); changes in these variables were not materially influenced by the choice of calcium preparation. No significant changes were recorded in mean right atrial pressure, heart rate or cardiac rhythm. For the same increase in [Ca2+], [Ca] increased more following calcium gluceptate than after calcium chloride (table II). Other biochemical variables did not change during the periods of observation."

Applicant's summary and conclusion

Conclusions:

The availability of Ca ion is higher after Ca glucoheptonate injections than after CaCl2 injections. Ca plasma concentrations increased more following calcium gluceptate than after calcium chloride injections.

Executive summary:

Calcium chloride and calcium gluceptate were compared in their ability to increase plasma ionized calcium concentrations ([Ca2+]). To correct a low ionized calcium concentration, each of 10 critically ill patients received both calcium chloride (10 ml of a 10% solution, containing elemental calcium 27 mg/mL) and calcium gluceptate (20 ml, containing elemental calcium 18 mg/mL) over a 5-min period in randomized order approximately 6 h apart. [Ca2+] and haemodynamic variables (mean arterial pressure (MAP), mean right atrial pressure (RAP) and heart rate (HR)) were monitored for a 30-min period following completion of calcium infusion. Infusion of either calcium preparation was associated with similar increases in [Ca2+] (5 min after infusion of calcium chloride: 33 ± 3.1%; calcium gluceptate: 32 + 4.3% (mean + SEM)) and the effects on MAP were similar for each solution (11.1 ± 1.8% and 9.7 + 2.4%, respectively).