Butylscopolamine Other names: Scopolamine butylbromide Hyoscine

Butylscopolamine is an antispasmodic agent which relaxes smooth muscle of the organs of the abdominal and pelvic cavities. It is believed to act predominantly on the intramural parasympathetic ganglia of these organs.

Butylscopolamine exerts a spasmolytic action on the smooth muscle of the gastrointestinal, biliary and genito-urinary tracts. As a quaternary ammonium derivative, butylscopolamine does not enter the central nervous system. Therefore, anticholinergic side effects at the central nervous system do not occur. Peripheral anticholinergic action results from a ganglion-blocking action within the visceral wall as well as from an anti-muscarinic activity.

Absorption

As a quaternary ammonium compound, butylscopolamine is highly polar and hence only partially absorbed following oral (8%) or rectal (3%) administration. After oral administration of single doses of butylscopolamine in the range of 20 to 400 mg, mean peak plasma concentrations between 0.11 ng/mL and 2.04 ng/mL were found at approximately 2 hours. In the same dose range, the observed mean AUC0-tz-values varied from 0.37 to 10.7 ng h/mL. The median absolute bioavailabilities of different dosage forms, i.e. coated tablets, suppositories and oral solution, containing 100 mg of butylscopolamine each were found to be less than 1%.

Distribution

Because of its high affinity for muscarinic receptors and nicotinic receptors, butylscopolamine is mainly distributed on muscle cells of the abdominal and pelvic area as well as in the intramural ganglia of the abdominal organs. Plasma protein binding (albumin) of butylscopolamine is approximately 4.4%. Animal studies demonstrate that butylscopolamine does not pass the blood-brain barrier, but no clinical data to this effect is available. butylscopolamine (1 mM) has been observed to interact with the choline transport (1.4 nM) in epithelial cells of human placenta in vitro.

Metabolism and elimination

Following oral administration of single doses in the range of 100 to 400 mg, the terminal elimination half-lives ranged from 6.2 to 10.6 hours. The main metabolic pathway is the hydrolytic cleavage of the ester bond. Orally administered butylscopolamine is excreted in the faeces and in the urine. Studies in man show that 2 to 5% of radioactive doses is eliminated renally after oral, and 0.7 to 1.6% after rectal administration. Approximately 90% of recovered radioactivity can be found in the faeces after oral administration. The urinary excretion of butylscopolamine is less than 0.1% of the dose. The mean apparent oral clearances after oral doses of 100 to 400 mg range from 881 to 1420 L/min, whereas the corresponding volumes of distribution for the same range vary from 6.13 to 11.3 × 105 L, probably due to very low systemic availability. The metabolites excreted via the renal route bind poorly to the muscarinic receptors and are therefore not considered to contribute to the effect of the butylscopolamine.

Paediatric population

No particular pharmacokinetic studies concerning butylscopolamine have been performed in children.

In limited reproductive toxicity studies butylscopolamine showed no evidence of teratogenicity in rats at 200 mg/kg in the diet or in rabbits at 200 mg/kg by oral gavage or 50 mg/kg by subcutaneous injection. Fertility in the rat was not impaired at doses of up to 200 mg/kg in the diet.