Sodium sulphate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Literature data

Data source

Reference

Reference Type:

publication

Title:

Absorption of Orally Administered Sodium Sulfate in Humans.

Author:

Cocchetto David M. and Levy Gerhard

Year:

1981

Bibliographic source:

Journal of Pharmaceutical Sciences / 331 Vol. 70, No. 3, March 1981

Materials and methods

Objective of study:

absorption

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Sodium sulphate

EC Number:

231-820-9

EC Name:

Sodium sulphate

Cas Number:

7757-82-6

Molecular formula:

Na2SO4

IUPAC Name:

disodium sulfate

Test animals

Species:

human

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- No of organisms: 5 healthy men.

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTION
Sodium sulfate was dissolved in 50 ml of warm water

Duration and frequency of treatment / exposure:

Test solution was administrate, either as a single dose or in four equally divided hourly doses.
Men received sodium sulfate orally on two occasions, at least 1 week apart.

Doses / concentrations

Remarks:

Doses / Concentrations:
Men received 18.1 g of sodium sulfate USP, the decahydrate, equivalent to 8.00 g of anhydrous sodium sulfate.

No. of animals per sex per dose / concentration:

5

Details on study design:

AFTER DOSE ADMINISTRATION
When men received sodium sulphate, the subjects fasted overnight and consumed a low fat breakfast in the morning.
They emptied their bladder before ingesting the test solution.

BEFORE DOSE ADMINISTRATION
Men ate lunch and their subsequent meals and fluid intake were not restricted or controlled.

Details on dosing and sampling:

- Tissues and body fluids sampled: all urine, for determination of baseline free sulfate output.
- Time and frequency of sampling: urine sample were collected for three separate 24-hr periods; over 0-24, 24-48 and 48-72 hr.
- Collection vessel: all urine was collected in sterile plastic bags.
- Sample storage: the urines were frozen immediately after collection, pending assay.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on excretion:

The baseline individual average excretion rate of inorganic sulfate ranged from 13 to 25 mmoles/24 hr and was relatively constant (coefficient of variation of 747%).The individuals with the lowest body weight (DC and SR) exhibited the lowest baseline values. Compared with the amount of sodium sulfate taken by the subjects (56.3 mmoles), the baseline excretion rate of inorganic sulfate was substantial.

The baseline excretion rate of free sulfate was not affected by relatively large changes in urine flow rate, but the baseline excretion rate of total sulfate (and therefore, of organically bound sulfate) increased essentially linearly with increasing urine flow rate. This differential effect of the urine flow rate also was observed after sodium sulfate administration.

The cumulative amounts of free sulfate excreted in the urine 24, 48 and 72 hr after sodium sulfate administration were significantly larger than the amounts of free sulfate excreted during the same lengths of time in control experiments (p < 0.01 by paired t test).
The average urinary recovery of administered sulfate, calculated as the 72-hr excretion of free sulfate minus the baseline excretion, averaged 53.4% from the single dose and 61.8% from the divided doses.
There was considerably less interindividual variation in urinary recovery of free sulfate from the divided doses.

Any other information on results incl. tables

Urinary Excretion of Free Sulfate by Normal Men after Oral Administration of 18 g of Sodium Sulfate Decahydrate (= 8 g sodium sulphate anhydrous) in Single and Divided Doses.

Subject	Age (y)	Bodi weight (kg)	Baseline Excretion rate (mmoles/24hr^*)	Cumulative Percent of dose excreted
				Single dose			Divided Dose^**
				24 hr	48 hr	72 hr	24 hr	48 hr	72 hr
PM	25	79	22.9 ± 2.9	24.5	27.1	38.8	37.2	49.7	57.2
DC	25	66	16.7 ± 1.2	40.7	62.9	71.5	44.6	52.8	63.2
DS	34	77	24.3 ± 6.5	55.2	65.3	68.9	48.3	60.0	69.3
UW	36	74	25.0 ± 6.4	44.4	49.0	39.4	59.8	60.4	68.4
SR	28	66	13.0 ± 2.1	17.3	43.0	48.5	27.9	42.5	50.8
Mean				36.4	49.5	53.4	43.5^***	53.1^***	61.8^***
SD				15.4	15.6	15.8	12.0	7.5	7.8

*Mean f SD, n = 3 consecutive days.

**Four equally divided doses administered at hourly intervals.

***Not significantly different ( p > 0.1) from corresponding value after single dose.

All subjects experienced severe diarrhea after the single dose of sodium sulfate, starting typically after 2 hr and lasting up to 24 hr. The same amount of sodium sulfate taken in four equal hourly doses produced either no diarrhea or mild diarrhea of short duration. No other adverse effects were reported.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
The cumulative amounts of free sulphate excreted in the urine 24, 48 and 72 hr after sodium sulphate administration were significantly larger than the amounts of free sulfate excreted during the same lengths of time in control experiments. The average urinary recovery of administered sulphate averaged 53.4% from the single dose and 61.8% from the divided doses.
The single dose produced severe diarrhea while the divided doses caused only mild or no diarrhea.

Executive summary:

The purposes of this investigation were to determine the absorption of a large amount of sodium sulfate (18.l g as the decahydrate, equivalent to 8.0 g of the anhydrous salt) and to compare the bioavailability when this amount is administered orally to normal subjects as a single dose and as four equally divided hourly doses.

Result

The cumulative amounts of free sulphate excreted in the urine 24, 48 and 72 hr after sodium sulphate administration were significantly larger than the amounts of free sulphate excreted during the same lengths of time in control experiments. The average urinary recovery of administered sulphate, calculated as the 72-hr excretion of free sulphate minus the baseline excretion, averaged 53.4% from the single dose and 61.8% from the divided doses.

The single dose produced severe diarrhea while the divided doses caused only mild or no diarrhea. Thus,a large amount of sodium sulphate, when administered orally in divided doses over 3 hr, is well tolerated and is absorbed to a significant extent.