Source: Medicines Authority (MT) Revision Year: 2020 Publisher: GlaxoSmithKline Consumer Healthcare Hellas Single Member Societe Anonyme, the distinctive title GSK CH Hellas Single Member S.A., 274 Kifissias Ave, 15232, Halandri, Athens, Greece
Pharmacotherpeutic group: R05DB13
Other antitussives/Butamirate
Butamirate citrate, the active ingredient of SINECOD, suppresses the cough without being chemicallyor pharmacologically related to opium alkaloids.
The substance is thought to have central action. The exact mechanism of action is unknown. Butamirate citrate presents a non-specific anticholinergic and antispasmodic effect which facilitates respiration . Sinecod does not induce dependence or addiction.
Butamirate citrate has a broad therapeutic range. It is well tolerated even at high doses and well suited for cough relief in adults and children. Butamirate citrate is a non-narcotic antitussive which acts at the centre of the cough. Unlike morphine products (narcotic antitussives), SINECOD lacks the risk of their side effects without lacking the antitussive action.
Butamirate when administered orally is absorbed quickly and completely. It is hydrolysed mainly into phenyl-2-butyric acid and diethylaminoethoxyethanol. The influence of food ingestion has not been investigated. Exposure to phenyl-2- butyric acid and diethylaminoethoxyethanol is fully proportional across the dose range of 22.5 mg – 90 mg.
When administered orally, butamirate is rapidly absorbed. It can be detected in the blood plasma within 5 to 10 minutes of administration of a 22.5 mg, 45 mg, 67.5 mg and 90 mg dose. Maximum plasma concentrations are reached after one hour for all four dose levels, with a mean value of 16.058 ng/ml at the dose of 90 mg.
The mean plasma concentration of phenyl-2-butyric acid is reached within 1.5 hours with the greatest exposure being observed after 90 mg (3.052 nanogram/mL). The mean plasma concentration of diethylaminoethoxyethanol is reached within 0.67 hour again with greatest exposure again being observed after 90 mg (160 nanograms/ml).
Distribution Butamirate has a high volume of distribution ranging between 81 and 112 L (depending on body weight in kg) as well as a high degree of protein binding. Phenyl-2-butyric acid is highly protein bound in plasma across all dose levels (22.5–90 mg) with mean values of 89.3% – 91.6%. Diethylaminoethoxyethanol exhibits some degree of protein binding with mean values ranging between 28.8%–45.7%. It is not known whether butamirate crosses the placenta or whether it is secreted in human milk.
The hydrolysis of butamirate, which leads mainly to phenyl-2-butyric acid and diethylaminoethoxyethanol, takes place immediately and completely. Based on studies in various species, it is concluded that the main metabolites have an antitussive effect. There are no human data on the alcoholic metabolite. Phenyl2-butyric acid undergoes further partial metabolisation through hydroxylation at position p.
The excretion of the three metabolites takes place primarily via the kidneys; following conjugation in the liver, the acid metabolite is subject to large-scale binding to glucuronic acid. Urinary 2-phenylbutyric acid conjugate levels are much higher than in plasma. Butamirate can be detected in the urine for up to 48 hours and the amount of butamirate excreted in urine over the 96-hour sampling period, accounts for approximately 0.02, 0.02, 0.03 and 0.03% of the 22.5 mg, 45 mg, 67.5 mg and 90 mg dose levels, respectively. A greater percentage of the butamirate dose is excreted in the urine in the form of diethylaminoethoxyethanol or unconjugated phenyl-2-butyric acid. The average measured half-lives of phenyl-2-butyric acid, butamirate, and diethylaminoethoxyethanol are 23.26–24.42, 1.48–1.93, and 2.72–2.90 hours, respectively.
There are no known effects of hepatic or renal function disorders on the pharmacokinetic parameters of butamirate.
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, toxicity to reproduction and development.
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