TENSOPYN Tablet Ref.[51217] Active ingredients: Caffeine Codeine Doxylamine Paracetamol

Paracetamol

Paracetamol is readily absorbed from the gastrointestinal tract with peak plasma concentrations occurring about 10 to 60 minutes after oral doses. Paracetamol is distributed into most body tissues. It crosses the placenta and is presented in breast milk. Plasma-protein binding is negligible at usual therapeutic concentrations but increases with increasing concentrations. The elimination half-life of paracetamol varies from about 1 to 3 hours. Paracetamol is metabolised predominantly in the liver and excreted in the urine mainly as the glucoronide and sulphate conjugates. Less than 5% is excreted as unchanged paracetamol. A minor hydroxylated metabolite (N-acetyl-p-benzoquinoneimine) is usually produced in very small amounts by cytochrome P450 isoenzymes in the liver and kidneys. It is usually detoxified by conjugation with glutathione but may accumulate following paracetamol overdosage and cause tissue damage.

Codeine phosphate

Codeine phosphate is absorbed from the gastrointestinal tract. Ingestion of codeine phosphate produces peak plasma-codeine concentrations in about one hour. Codeine phosphate is metabolized by 0- and N-demethylation in the liver to morphine, norcodeine, and other metabolites including normorphine and hydrocodone. Codeine phosphate and its metabolites are excreted almost entirely by the kidneys, mainly as conjugates with glucuronic acids. The plasma half-life has been reported to be between 3 and 4 hours after an oral dose.

Caffeine

Caffeine is absorbed readily after oral doses and is widely distributed throughout the body. Caffeine passes readily into the CNS and into saliva; low concentrations are also present in breast milk. Caffeine crosses the placenta.

In adults, caffeine is metabolised almost completely in the liver via oxidation, demethylation, and acetylation and is excreted in the urine as 1-methyluric acid, 1-methylxanthine, 7-methylxanthine, 1,7-dimethylxanthine (paraxanthine), 5-acetylamino-6-formylamino-3-methyluracil (AFMU), and other metabolites with only about 1% unchanged. Hepatic cytochrome P450 isoenzyme CYP1A2 is involved in caffeine enzymatic metabolism. Elimination half-lives are about 3 to 7 hours in adults. The metabolism of caffeine has been shown to be dose dependent with clearance decreasing as the dose is increased suggesting saturable metabolism. Four- to five-fold differences in plasma half-lives of caffeine are common among healthy people. The plasma half-life of caffeine is decreased by smoking and by exercise and is increased by liver disease such as cirrhosis and viral hepatitis, and in pregnancy. The plasma half-life of caffeine is not affected by old age or obesity. Drug interactions also affect the pharmacokinetics of caffeine.

Doxylamine succinate

Peak plasma concentrations of doxylamine succinate occur 2 to 3 hours after oral doses. An elimination half-life of about 10 hours has been reported.