Levosulpiride

Biochemical, pharmacological and clinical data obtained with the two isomers of sulpiride, indicate that the antidopaminergic activity, both at central and local levels, is due to levo-rotatory enantiomer.

When levosulpiride is administered orally at a dose of 50 mg, the peak plasma concentration is reached in 3 hours, in an average of 94.183 ng/ml.

The t_½ of elimination calculated after administration of 50 mg iv of levosulpiride is 4.305 hours.

The elimination of the medicine occurs mainly via the urine.

The values expressed as LD₅₀ acute toxicity after oral administration in mice, rats and rabbits were 2450 mg/kg, 2600 mg/kg and greater than 1500 mg/kg.

LD₅₀ values:

• in the mouse: 210 mg/kg, via i.p,
• in the rat via i.p. and i.v.: to 270 mg/kg and 53 mg/kg, respectively,
• in the rabbit via i.v.: to 42 mg/kg.

Subacute toxicity tests were conducted by administering the active ingredient in rat, rabbit and dog, daily, for 12-13 weeks. The appearance of any toxic symptoms was not observed at doses of:

• 25 mg/kg sc and 300 mg/kg p.o. in the rat,
• 250 mg/kg p.o. and 12.5 mg/kg i.m. in rabbits,
• 50 and 100 mg/kg p.o. in the dog.

To evidentiate the chronic toxicity following administration of the drug for 180-190 days, doses of:

• 100 mg/kg p.o. and 20 mg/kg s.c. in the rat,
• 10 mg/kg i.m. in rabbits and
• 20 mg/kg p.o. in the dog, were well tolerated.

Studies performed in rats and mice, administering the medicine at a dose higher than that expected for man, have shown that levosulpiride do not possess carcinogenic properties.

Studies carried out in rats and rabbits have shown that the medicine is not teratogenic.

In vitro tests have ruled out that the medicine possesses mutagenic properties.