Potassium hydrogen oxalate

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:

other information

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The experimental setup does not make use of a guideline setup. There is no data on the application of GLP principles.

Data source

Reference

Reference Type:

publication

Title:

Plasma Oxalate Concentration and Renal Excretion of Oxalate in Man

Author:

Hodgkinson, A., Wilkinson, R.

Year:

1974

Bibliographic source:

Clinical Science and Molecular Medicine, Vol. 46, pp 61 - 73

Materials and methods

Type of study / information:

Study using 3 male volunteers and 15 male patients with recurring calcium oxalate or mixed calcium oxalate - calcium phosphate stones

Endpoint addressed:

not applicable

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

In an attempt to resolve the tenfold difference in plasma oxalate levels, as determined by chemical and isotopic methods, the plasma oxalate levels were established by another isotopic method involving the simultaneous measurement of [14C]oxalate activities in plasma and urine and the concentration of stable oxalate in the urine. Measurements have been made of the exchangeable oxalate pool and of the renal clearance of oxalate in normal adults and patients with calcium oxalate-containing renal stones. The effect of the uricosuric agent, probenecid, on the renal excretion of oxalate has also been examined.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

[14C] oxalic acid

IUPAC Name:

[14C] oxalic acid

Details on test material:

- Name of test material (as cited in study report): [14C] oxalic acid

- Radiochemical purity (if radiolabelling): (45.2 µCi/,umo1 of oxalic acid, or 359 µCi/ing of oxalic acid dihydrate)

- Locations of the label (if radiolabelling): Uniformly labelled

Method

Details on study design:

Each subject fasted from 21.00 hours on the day before the investigation until 2 h after administration of the radioisotope, after which normal foods and fluid were allowed. Timed urine collections were made before and after administration of the radioisotope and blood samples were collected into heparinized tubes at the mid-point of each urine collection period.
Uniformly labelled [14C]oxalic acid of high specific radioactivity (45.2 µCi/,umo1 of oxalic acid, or 359 µCi/ing of oxalic acid dihydrate) was obtained from The Radiochemical Centre, Amersham, England, and 2 uCi was administered intravenously in 2 ml of sterile sodium chloride solution (0.15 mol/1) or orally in 250 ml of distilled water containing 0.22 µmol (30 mg) of sodium oxalate. 14C radioactivity was measured by mixing 4 ml of plasma or urine with a gelled liquid-scintillation medium (Oxby & Kirby, 1968) and counted in a Philips, type P.W. 4510/D, automatic liquid-scintillation analyser. Activity was expressed as a percentage of the administered dose of 14C/litre of plasma or urine, after appropriate correction for quenching and
background.

Exposure assessment:

measured

Results and discussion

Results:

1. The concentration of oxalate in plasma was determined by an isotopic method involving the simultaneous measurement of [14C]oxalate activities in plasma and urine and the concentration of stable oxalate in the urine.

2. Plasma oxalate concentrations ranged from 1-3 to 1-6 µmol/1 (11.8-14.3 µg/100 ml) in three normal men; in fifteen male patients with renal calcium oxalate stones the mean value was 1.73 pmol/l (15.6 ,ug/100 ml), SD = 0.55 µmol/1 (4.98 µg/100 ml).

3. The renal clearance of [14C] oxalate ranged from 162 to 3581 n1/min (mean = 249 ml/min) in the normal subjects and from 95 to 315 ml/min (mean = 201 ml/min) in the patients. A direct and statistically significant relationship was observed between the oxalate and creatinine clearances.

4. The oxalate/creatinine clearance ratio ranged from 1.42 to 2.60 (mean = 1.95) in the normal subjects and from 1.04 to 2.33 (mean = 1.76) in the patients, implying a net renal tubular secretion of oxalate. However, oxalate excretion was unaffected by probenecid, a drug known to inhibit the active tubular transport of organic anions,

5. Possible errors in the determination of plasma oxalate concentration and oxalate clearance by chemical and isotopic methods are discussed.

6. Intravenous administration of [14C]oxalate to eight subjects allowed estimations of the miscible oxalate pool [mean = 53.3 µmol (4.80 mg); SD = 18.7,umol (1.68 mg)], the volume of distribution of [14C]oxalate (mean = 45.2% of body weight; SD = 5-65) and the biological half-life of [14C]oxalate (mean = 91.10 min; SD = 13.89).

Applicant's summary and conclusion

Conclusions:

no definite conclusions were based on the current study.

Executive summary:

1. The concentration of oxalate in plasma was determined by an isotopic method involving the simultaneous measurement of [14C]oxalate activities in plasma and urine and the concentration of stable oxalate in the urine.

2. Plasma oxalate concentrations ranged from 1-3 to 1-6 µmol/1 (11.8-14.3 µg/100 ml) in three normal men; in fifteen male patients with renal calcium oxalate stones the mean value was 1.73 pmol/l (15.6 ,ug/100 ml), SD = 0.55 µmol/1 (4.98 µg/100 ml).

3. The renal clearance of [14C] oxalate ranged from 162 to 3581 n1/min (mean = 249 ml/min) in the normal subjects and from 95 to 315 ml/min (mean = 201 ml/min) in the patients. A direct and statistically significant relationship was observed between the oxalate and creatinine clearances.

4. The oxalate/creatinine clearance ratio ranged from 1.42 to 2.60 (mean = 1.95) in the normal subjects and from 1.04 to 2.33 (mean = 1.76) in the patients, implying a net renal tubular secretion of oxalate. However, oxalate excretion was unaffected by probenecid, a drug known to inhibit the active tubular transport of organic anions,

5. Possible errors in the determination of plasma oxalate concentration and oxalate clearance by chemical and isotopic methods are discussed.

6. Intravenous administration of [14C]oxalate to eight subjects allowed estimations of the miscible oxalate pool [mean = 53.3 µmol (4.80 mg); SD = 18.7,umol (1.68 mg)], the volume of distribution of [14C]oxalate (mean = 45.2% of body weight; SD = 5-65) and the biological half-life of [14C]oxalate (mean = 91.10 min; SD = 13.89).