Indometacin

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: acceptable well documented study report which meets basic scientific principles

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1976

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Radio-labeled indometacin and acemetacin (with 14-C) were applied to male rats by the oral, intravenous and intraduodenal route in equimolar dosages. Radioactivity was measunred in excreta, secretions and tissues.

Test material

Test material information

Constituent 1

Reference substance name:

Indometacin

EC Number:

200-186-5

EC Name:

Indometacin

Cas Number:

53-86-1

Molecular formula:

C19H16ClNO4

IUPAC Name:

2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid

Details on test material:

test material radiolabeled with 14-C; , 30µCi/mg, radiochemical purity: > 99%

Radiolabelling:

yes

Remarks:

14-C

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Administration / exposure

Route of administration:

oral: gavage

Duration and frequency of treatment / exposure:

single administration

Doses / concentrations

Remarks:

Doses / Concentrations:
5 mg/kg bw (2 mL/animal)

No. of animals per sex per dose / concentration:

5

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Resorption was 80% or more

Details on distribution in tissues:

One hour after oral administration, 50-60% of radioactivity (less gastrointestinal tract) was in the animal. The highest concentration was in serum. Six hours after administration, high concentrations were seen in liver, kidney and still serum. Low concentrations occurred in brain and musculature. Relatively high activity in serum indicates a low volume of distribution of test material and metabolites. Whole body autoradiography after 3 min, and 1,3, and 6 hours confirmed the distribution pattern and revealed transient accumulation in brown adipose tissue, collagen connective tissue and salivary gland at the throat.

Details on excretion:

Within 48 hours after oral and intravenous administration 30-40 of radioactivity was renally eliminated, about 6% of acitivity was metabolized to 14-C-carbondioxide. The rest (approx. 55-60%) was eliminated by the feces. After 48 hours, 1-2% of radioactivity remain in the animal (gastro-intestinal tract not included). After intraduodenal administration, the resorbed activity was mainly eliminated via bile and partly re-resorbed, showing enterohepatic circulation.