Chemical formula: C₁₈H₂₉NO₃ Molecular mass: 307.434 g/mol
Butamirate citrate exerts antitussive action and is not chemically or pharmacologically related to the opioid alkaloids. It is considered that butamirate citrate is a centrally acting drug but the exact mechanism of action is not known. It exerts non-specific anticholinergic and bronchospasmolytic effects thereby improving respiratory function.
Butamirate does not induce tolerance or dependence. It has a wide therapeutic index; it is well tolerated in high doses and suitable for cough relief in children and adults.
It can be estimated from available data, that butamirate ester is absorbed well and rapidly. It is completely hydrolysed to 2-phenylbutyric acid and diethylaminoetoxyethanol. Effect of food intake has not been studied. Exposition of 2-phenylbutyric acid and diethylaminoetoxyethanol is proportional in all dosage range.
After oral administration butamirate is rapidly absorbed. Measurable level have been detected in blood after 5 to 10 minutes after first dose of 22.5 mg, 45 mg, 67.5 mg and 90 mg. The peak plasma concentration is reached within 1 hour for all 4 dose levels with average level 16.1 ng/ml for 90 mg dose.
The average plasma level of 2-phenylbutyric acid, is reached after 1.5 hours with peak level detected after administration 90 mg (3052 ng/ml). The average plasma level of diethylaminoetoxyethanol, is reached after 0.67 hour with peak level detected after administration 90 mg (160 ng/ml).
The volume of distribution of butamirate is large, 81-112 L (counted per body weight in kg) and also butamirate is highly bound to plasma proteins. 2-phenylbutyric acid is bound highly bounded to plasma proteins in all dose levels (22.5 mg-90 mg) with average level 89.3%-91.6%. Diethylaminoetoxyethanol shows some binding level to plasma proteins with average level 28.8%-45.7%. It is not known whether the substance passes through the placental barrier and is excreted in human milk.
Butamirate is rapidly and fully hydrolysed mainly into 2-phenylbutyric acid and diethylaminoetoxyethanol. In experiments on different animal species, the two major metabolites have been shown to exhibit also a cough-soothing effect. Data for alcohol-like metabolite is not known in humans. 2-phenylbutyric acid is partially metabolised by hydroxylation at the para-position.
Three metabolites are extracted via kidney, after conjugation after subsequent conjugation in the liver, the acidic metabolites of butamirate connect largely with glucuronic acid. The level of 2-phenylbutyric acid conjugates are much higher in urine than in plasma. Butamirate has been detected in urine after 48 hours and amount of excreted butamirate has been monitored in 96 hours intervals and has corresponded to levels 0.02%, 0.02%, 0.03%, and 0.03% after administration of 22.5 mg, 45 mg, 67.5 mg and 90 mg, respectively. Most of butamirate is excreted in urine in form of diethylaminoetoxyethanol or notconjugated 2-phenylbutyric acid. It has been found that the average elimination half-life time of 2-phenylbutyric acid, butamirate and diethylaminoetoxyethanol is 23.26-24.42 hours, 1.48-1.93 hours, 2.72-2.90 hours, respectively.
It is not known whether liver or renal dysfunction has an impact on pharmacokinetic parameters of butamirate.
Animal studies and in vitro experiments based on acute, repeated dose toxicity, toxicity to reproduction and mutagenicity of butamirate reveal no hazard for humans within the therapeutic use of the product.
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