Tienilic acid

Tienilic acid is a uricosuric diuretic. Tienilic acid possesses certain hepatotoxicity[1][3].

Signaling Pathways >> Others >> Others

Research Areas >> Metabolic Disease

Tienilic acid (100 mg/lg in rats and mice, 5 mg/kg in pigs and dog; PO and IV; single dosage) is only found in plasma, eliminates by the biliary and the urinary fast, and exhibits small differences in the different species[2]. Tienilic acid (0-480 mg/kg; PO; for 28 days) decreases blood pressure, serum, uric acid hemoglobin, and increased S-GPT; induces unicellular necrosis of small groups of liver cells[3]. Animal Model: Rats, mice, pigs and dogs[2] Dosage: 100 mg/lg in rats and mice, 5 mg/kg in pigs and dogs Administration: PO and IV; single dosage Result: Only found in plasma with important bindings to the plasma proteins at the blood level; pharmacological action for several hours; eliminated by the biliary and particularly the urinary fast, practically total in the first 48 hours after administration; only small differences were observed for the parameters measured in the different species. Animal Model: Female and male Sprague-Dawley rats[3] Dosage: 0, 30, 120 and 480 mg/kg Administration: PO; for 28 days Result: Decreased blood pressure and serum uric acid at 30 mg/kg; decreased slightly hemoglobin and increased S-GPT at 120 and 480 mg/kg; significantly increase the liver weight and serum magnesium concentration in male rats, while the liver weight of female rats increased only slightly; besides, induced unicellular necrosis of small groups of liver cells.

[1]. Lemieux G, et al, Baverel G. Metabolic effects in man of tienilic acid, a new diuretic with uricosuric properties. Nephron. 1978;20(1):54-64.

[2]. Levron, J.C., et al. Pharmacokinetic study of 2,3-dichloro 4- (2-thienyl keto14C) phenoxyacetic acid (tienilic acid) in animals. European Journal of Drug Metabolism and Pharmacokinetics 2, 107–120 (1977).

[3]. Oker-Blom C, et al. Toxicological studies on tienilic acid in rats. Toxicol Lett. 1980;6(2):93-99.

DATA ITEMS CITED :

10

MOLECULAR FORMULA :

C13-H8-Cl2-O4-S

MOLECULAR WEIGHT :

331.17

WISWESSER LINE NOTATION :

T5SJ BVR BG CG DO1VQ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

3571 ug/kg

TOXIC EFFECTS :

Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Kidney, Ureter, Bladder - urine volume decreased

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

6666 ug/kg

TOXIC EFFECTS :

Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

5 mg/kg

TOXIC EFFECTS :

Gastrointestinal - nausea or vomiting Kidney, Ureter, Bladder - urine volume decreased

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1275 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

318 mg/kg

TOXIC EFFECTS :

Kidney, Ureter, Bladder - urine volume increased

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

225 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

3360 mg/kg/28D-I

TOXIC EFFECTS :

Vascular - BP lowering not characterized in autonomic section Liver - changes in liver weight Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

6300 mg/kg/14D-I

TOXIC EFFECTS :

Liver - other changes Kidney, Ureter, Bladder - other changes Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - hepatic microsomal mixed oxidase (dealkylation, hydroxylation, etc.)

MUTATION DATA

TYPE OF TEST :

Mutation in mammalian somatic cells

TEST SYSTEM :

Rodent - hamster Lung

DOSE/DURATION :

100 umol/L

REFERENCE :

MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 157,1,1985