Magnesium hydroxide

Exposure related observations in humans: other data

Administrative data

Endpoint:

exposure-related observations in humans: other data

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1987

Materials and methods

Endpoint addressed:

basic toxicokinetics

acute toxicity: oral

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test: Examination of the bioavailability of magnesium following a large oral dose of magnesium sulphate in volunteers.
- Short description of test conditions: Seven healthy men who had not taken any medication for at least a week were chosen for this study and administered a cathartic dose of magnesium sulphate orally. Urinary excretion of magnesium was then monitored over a 72-hour period. Urine samples were collected at approximately 4-hour intervals during the day and over 8 hours at night.
- Parameters analysed / observed: Baseline 24-hour excretion rates were calculated for each subject by averaging the results of each of the 3 consecutive 24-hour urine collections during the control week.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Magnesium sulphate

EC Number:

231-298-2

EC Name:

Magnesium sulphate

Cas Number:

7487-88-9

Molecular formula:

H2O4S.Mg

IUPAC Name:

Magnesium Sulphate

Specific details on test material used for the study:

Magnesium sulphate, USP was administered. This is the heptahydrate salt. It is equivalent to 6.8 g of anhydrous salt, or 56.5 mmoles.

Method

Ethical approval:

not specified

Details on study design:

Seven healthy men who had not taken any medication for at least a week were chosen for this study and administered a cathartic dose of magnesium sulphate orally. Urinary excretion of magnesium was then monitored over a 72-hour period. Urine samples were collected at approximately 4-hour intervals during the day and over 8 hours at night. They were frozen immediately.

For assay, the samples were allowed to defrost, and then they were shaken. They were centrifuged for 2 minutes. The supernatant was diluted and then assayed by atomic absorption spectrophotometry. The precipitate was dissolved in 1N HCl and the mean magnesium content was determined.

Baseline 24-hour excretion rates were calculated for each subject by averaging the results of each of the 3 consecutive 24-hour urine collections during the control week. These could then be subtracted from the results obtained during the experimental week to correct for endogenous magnesium.

Exposure assessment:

measured

Details on exposure:

TYPE OF EXPOSURE: oral

During the experimental week, subjects received 13.9 g magnesium sulfate, USP (the heptahydrate salt, equivalent to 6.8 g of anhydrous salt, or 56.5 mmoles) in four divided portions of 3.48 g in 100 mL water at one-hour intervals after a light, low-fat breakfast. During the control week, the subjects received only the four aliquots of 100 mL water at one-hour intervals. The order of the treatment and control weeks was randomized.

Results and discussion

Results:

About 4% of 56.5 mmol (13.9 g) oral dose of magnesium sulfate is absorbed in healthy volunteers. All of the subjects experienced mild or moderate diarrhea. Therefore, magnesium is absorbed to a limited and variable extent in healthy adults following a cathartic dose of magnesium sulfate.

Any other information on results incl. tables

The urine from one subject was lost during transit and sample work-up.

The baseline excretion rate of magnesium for the remaining six subjects was (mean±SD) 4.4±1.1 mmoles/day (range of means: 3.0-6.0) with a coefficient of variation (based on the

three control days) of 21.3±8.72 (range: 9.1-31.7%). Creatinine excretion rates ranged from 12.4 to 18.7 mmoles/day with a coefficient of variation for individual subjects of 9.4±4.8%.

Baseline magnesium excretion rates were significantly correlated with baseline creatinine excretion rates (r=0.875, p<0.05). The intersubject variability in the 24-hour excretion rate of magnesium was not significantly reduced by normalizing the baseline excretion rate for either body weight or estimated body surface area (not reported) but was decreased when magnesium excretion rates were normalized for creatinine excretion rates.

The urinary excretion of magnesium during the first 24 hours after administration of magnesium sulfate, corrected for baseline excretion, was 4.0±2.9% of the dose (range: 0.8-8.7%). The cumulative average of the 48-hour and 72-hour periods were 5.9±4.7% and 6.9±7.0%, respectively. The 24-hour excretion rate of magnesium was significantly increased in 5 of the 6 subjects after magnesium sulfate ingestion. The excretion rate of creatinine during the treated period was essentially identical with that of the baseline value (mean±SD of individual excretion rate ratios, 1 .0±0.1).

The increase in the urinary excretion rates of magnesium after the ingestion of magnesium sulphate allows an estimation of the extent of absorption of this ion. While only 4.0±2.9% of the dose of magnesium was absorbed, 30.2±17.2% of the dose of inorganic sulphate was absorbed. All six subjects reported adverse gastrointestinal effects after magnesium sulphate ingestion. Two subjects experienced mild while four subjects experienced more severe diarrhea that began 3 to 11 hours after magnesium sulphate ingestion.

Table 1: Comparison of the Urinary Excretion of Magnesium and Sulfate after Oral Administration of 13.9 g Magnesium sulphate

Variable	Magnesium		Sulphate
Number of subjects	6		7
	mean	SD	mean	SD
Age	28.2	6.7	28.7	6.3
Body weight	77.1	5.4	75.8	6.0
Baseline Excretion Rate
(mmol/day)	4.4	1.0	23.8	4.2
(mmol/70 kg/day)	4.0	0.9	22.0	3.8
Baseline Excretion Ratio, ion/creatinine	0.27	0.03	1.5	0.14
Cumulative Excretion of Ions (%of Dose)
24 hours	4.0	2.9	30.2	17.2
48 hours	5.9	4.7	35.4	24.6
72 hours	6.9	7.0	37.5	26.9

Table 2: Individual 24 -Hour Urinary Excretion Rates of Magnesium after Oral Administration of 13.9 g Magnesium sulphate(a)

	Magnesium Excretion(b) (mmol/day)		Urinary Magnesium/Creatinine Ratio
Subject	Baseline	Treated	Baseline	Treated
1	3.8 (0.7)	4.7(c)	0.26 (0.02)	0.33(c)
2	4.7 (0.8)	5.1	0.28 (0.05)	0.29
3	3.0 (0.9)	5.3(c)	0.25 (0.08)	0.38(c)
4	6.0 (1.9)	10.9(c)	0.33 (0.11)	0.62(c)
5	4.5 (0.4)	7.9(c)	0.24 (0.01)	0.46(c)
6	4.5 (0.9)	6.3(c)	0.26 (0.05)	0.36(c)

(a) Results expressed as mean (SD)

(b) Amount excreted in the first 24 hours after magnesium sulphate

(c) Significantly different from baseline (p<0.05) by a two-tailed Z-test.

Applicant's summary and conclusion

Conclusions:

About 4% of 56.5 mmol (13.9 g) oral dose of magnesium sulfate is absorbed in healthy volunteers. All of the subjects experienced mild or moderate diarrhea. Therefore, magnesium is absorbed to a limited and variable extent in healthy adults following a cathartic dose of magnesium sulfate.

Executive summary:

In a publication from Morris et al., the bioavailability of magnesium following magnesium sulphate in normal volunteers was examined. Seven healthy men who had not taken any medication for at least a week were chosen for this study and administered a cathartic dose of magnesium sulphate orally. Urinary excretion of magnesium was then monitored over a 72-hour period. Urine samples were collected at approximately 4-hour intervals during the day and over 8 hours at night. Baseline 24-hour excretion rates were calculated for each subject by averaging the results of each of the 3 consecutive 24-hour urine collections during the control week.

About 4% of 56.5 mmol (13.9 g) oral dose of magnesium sulfate is absorbed in healthy volunteers. All of the subjects experienced mild or moderate diarrhea. Therefore, magnesium is absorbed to a limited and variable extent in healthy adults following a cathartic dose of magnesium sulfate.