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Non-Steroidal Anti-inflammatory and Antirheumatic/Analgesic.
Pharmacology: Pharmacodynamics: Aceclofenac is well absorbed from the gastrointestinal tract, peak plasma concentrations are reached 1 to 3 hours after an oral dose.
Plasma-elimination half-life is about 4 hours. About two-thirds of a dose is excreted in the urine, mainly as hydroxy metabolites. A small amount is converted to diclofenac.
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 present 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 mainly in the liver and excreted in the urine mainly as the glucuronide and sulfate conjugates. Less than 5% is excreted as unchanged Paracetamol. A minor hydroxylated metabolite (N-acetyl-p-benzoquinone imine), is usually produced in very small amounts by cytochrome P450 isoenzymes (mainly CYP2E1 and CYP3A4) in the liver and kidney. It is usually detoxified by conjugation with glutathione but may accumulate after Paracetamol overdosage and cause tissue damage.
Pharmacokinetics: Absorption: Aceclofenac: Rapidly absorbed; almost 100% bioavailability; peak plasma levels reached about 1.25-3 hr after oral admin.
Distribution: Aceclofenac: >99.7% bound to plasma proteins; distributes into synovial fluid.
Paracetamol: Distributes throughout most fluids of the body.
Metabolism: Aceclofenac: Probably metabolised by CYP2C9; average plasma elimination half-life: 4-4.3 hr.
Paracetamol: Mainly metabolised hepatically; plasma elimination half-life: 1-4 hr.
Excretion: Aceclofenac: About two-thirds of the administered dose is removed in the urine, mainly as conjugated hydroxy metabolites.
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