Potassium formate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Absorption and elimination of formate following oral administration of calcium formate in female human subjects

Author:

Hanzlik RP, Fowler SC, and Eells JT

Year:

2005

Bibliographic source:

Drug Metabolisn and Disposition 33, 282-286

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 417 (Toxicokinetics)

Deviations:

yes

Remarks:

; absorption and excretion in human subjects following a single oral fixed dose

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Calcium diformate

EC Number:

208-863-7

EC Name:

Calcium diformate

Cas Number:

544-17-2

Molecular formula:

CH2O2.1/2Ca

IUPAC Name:

calcium diformate

Details on test material:

- Name of test material (as cited in study report): calcium formate
- Substance type: salt
- Physical state: solid
- Other:
Calcium formate (650 mg/capsule) and placebo capsules were custom formulated by Opti-Med inc., Seymour, IN, USA)

Specific details on test material used for the study:

- Name of test material (as cited in study report): calcium formate
- Substance type: salt
- Physical state: solid
- Other:
Calcium formate (650 mg/capsule) and placebo capsules were custom formulated by Opti-Med inc., Seymour, IN, USA)

Radiolabelling:

no

Test animals

Species:

human

Strain:

other: not applicable

Sex:

female

Details on test animals or test system and environmental conditions:

Human subjects attending the study:
- Status: normal, healthy adults
- Sex: female
- Number: 14
- Age: between 19 and 33 years of age
- Body weight: mean 64.5 +/-11.2 kg.; range 51-93 kg
- Pregnant or breastfeeding: none

- Fasting: 10 hours overnight
- Drinking: subjects were allowed water ad libitum during the 4.5 hours after dosing

Administration / exposure

Route of administration:

oral: capsule

Vehicle:

water

Details on exposure:

Dosing:
- Subjects ingested either placebo or calcium formate
- Doses: 0 (placebo) or 3900 mg CaFo (6 capsules, 350 mg each)
- Vehicle: 240 mL water was ingested along with the capsules

Duration and frequency of treatment / exposure:

single oral dose

Doses / concentrations

Dose / conc.:

3 900 other: mg

Remarks:

mean dose: 60 mg CaFo/kg bw.

No. of animals per sex per dose / concentration:

14

Control animals:

yes, sham-exposed

Details on study design:

- Dose selection rationale: based on previous studies by Malorny (1969) and a preliminary study with 6 adult male volunteers (total 4550 mg/person)

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: blood
- Time and frequency of sampling: time 0, and at 30, 60, 90, 135, 180, 225, and 270 min after dosing

Statistics:

Pharmacokinetic analyses were performed using Excel X. Elimination rate constants (kel) were calculated as minus the slope of a plot of lnC versus time, and half-lives (t1/2) from the relationship t1/2 = ln2/kel. AUC values were calculated by trapezual integration. Oral clearance and apparent volumes of distribution were calculated as (CL/F=dose/delta AUC) and (Vß/F=(CL/F) / kel, respectively, where delta AUC refers to the increment in formate AUC above the baseline area. Results are reported as mean +/- SD (report, table 1).

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Calcium formate was rapidly absorbed. Maximal formate plasma levels (mean: 0.50 +/- 0.04 mmolar) were seen at 60 min after dosing.

Details on distribution in tissues:

No other tissue examined. The mean apparent distribution volume of 2.36 L/kg body weight indicates that the distribution in tissues follows the water solubility.

Details on excretion:

A monoexponential decline of serum concentrations with an average half-life of 59+/-7 minutes was seen to occur after 60 minutes post dosing. Baseline levels were reached by 225 minutes post dosing. The AUC was 49.4 +/- 6.2 mM x min, of this, 8.7+/-2.0 mM x min were attributable to endogenous formate. Thus, the net AUC resulting from 3900 mg of calcium formate was 41.2 +/-5.8 mM x min. From this and the formate dose given (60 mmol/subject) the oral clearance was (CL/F=1.95 L/min), and from this and the apparent elimination rate constant, the distribution volume was 156+/-27 liters, or 2.36+/-0.38 L/kg body weight.

Toxicokinetic parameters

Toxicokinetic parameters 1

Test no.:

#1

Toxicokinetic parameters:

half-life 1st: 59 +/- 7 minutes

Toxicokinetic parameters 2

Test no.:

#1

Toxicokinetic parameters:

Cmax: 0.50 +/- 0.04 mM

Toxicokinetic parameters 3

Test no.:

#1

Toxicokinetic parameters:

Tmax: 60 minutes

Toxicokinetic parameters 4

Test no.:

#1

Toxicokinetic parameters:

AUC: 41.2 +/-5.8 mM x min (net)

Toxicokinetic parameters 5

Test no.:

#1

Toxicokinetic parameters:

AUC: 8.7+/-2.0 mM x min (endogenous formate)

Toxicokinetic parameters 6

Test no.:

#1

Toxicokinetic parameters:

other: distribution volume: 2.36+/-0.38 L/kg body weight

Metabolite characterisation studies

Metabolites identified:

no

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
Calcium formate was rapidly absorbed, metabolised and eliminated in female human subjects ingesting 3900 mg calicum formate.

Executive summary:

Blood samples were withdrawn from 14 healthy female adult subjects (19 to 33 years of age; mean body weight 64.5 kg) following ingestion of placebo and a total of 3900 mg calcium formate at 0, and at 30, 60, 90, 135, 180, 225, and 270 min after dosing. Serum formate concentration was measured using a fluorometric assay.  

The maximal serum levels (mean: 0.50 mM) was seen at 60 minutes after dosing, and a monoexponential decline of serum concentrations with an average half-life of 59+/-7 minutes thereafter. Baseline levels (placebo) were reached by 225 minutes post dosing. The AUC was 49.4 +/- 6.2 mM x min, of this, 8.7+/-2.0 mM x min were attributable to endogenous formate. Thus, the net AUC resulting from 3900 mg of calcium formate was 41.2 +/-5.8 mM x minute. From this and the formate dose given (60 mmol/subject) the oral clearance was (CL/F = 1.95 L/min), and from this and the apparent elimination rate constant, the distribution volume was 156+/-27 liters, or 2.36+/-0.38 L/kg body weight.  

The results indicate that calcium formate was rapidly absorbed,metabolised and eliminated after oral ingestion by female human subjects, and that formate does not have an accumulation potential (Hanzlik; 2005)  

The study was conducted similar to provisions of the OECD guideline No. 417, and is considered to be valid for assessment.