DIHYDROCODEINE TRIFLUOROACETATE

Absorption

Bioavailability is low (approximately 20%) if administered orally. This may be due to poor gastrointestinal absorption. It is also likely due to pre-systemic metabolism by the liver and intestinal wall. [2]
The AUCs after oral and intravenous administration are similar (3203ug/l/h and 3401ug/l/h, respectively). [2]
Time to peak values are 1.6 and 1.8hours for a 30mg and 60mg dose, respectively. The concentrations achieved were 71.8 ug/1 and 146 ug/1, respectively. [2]

Originator

Bicodein,Uquifa

Background

Dihydrocodeine is an opioid analgesic used as an alternative or adjunct to codeine to treat moderate to severe pain, severe dyspnea, and cough.
It is semi-synthetic, and was developed in Germany in 1908 during an international search to find a more effective antitussive agent to help reduce the spread of airborne infectious diseases such as tuburculosis. It was marketed in 1911.

Indications

Dihydrocodeine is used for the treatment of moderate to severe pain, including post-operative and dental pain [2]. It can also be used to treat chronic pain [1], breathlessness and coughing.
In heroin addicts, dihydrocodeine has been used as a substitute drug, in doses up to 2500mg/day to treat addiction. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014322/]

Definition

ChEBI: Dihydrocodeine is a morphinane alkaloid.

Manufacturing Process

The codein was reduced by hydrogen in the presence catalyst Pt (or Pd, or Ni) and 7,8-dihydrocodein was obtained.
To the 7,8-dihydrocodein tartaric acid was added and mixed, in the result 7,8- dihydrocodein bitartrate was obtained.

Therapeutic Function

Antitussive, Narcotic analgesic

Pharmacokinetics

Possible opioid related side effects include, but are not limited to, drowsiness, nausea, headache, dry mouth, constipation, difficulty passing urine, and mild euphoria.

Safety Profile

Poison by ingestion, intravenous, and subcutaneous routes. Human systemic effects by ingestion and subcutaneous routes: somnolence, miosis (pupillary constriction), and respiratory depression. An analgesic. Can cause drug dependency with repeated doses. When heated to decomposition it emits toxic fumes of NOx. See also CODEINE.

Metabolism

Metabolized in the liver by CYP 2D6 into an active metabolite, dihydromorphine, and by CYP 3A4 into secondary primary metabolite, nordihydrocodeine. A third primary metabolite is dihydrocodeine-6-glucuronide. [1]
The time for mean peak concentration in acid metabolites is 1.76h and 1.98h for a 30 and 60mg dose, respectively. The concentrations achieved were 563 ug/1 and 1476 ug/1, respectively. [2]