Propacetamol
Propacetamol Uses, Dosage, Side Effects, Food Interaction and all others data.
Propacetamol is a non-opioid analgesic devoid of the major contraindications. It is a derivative of acetaminophen, or paracetamol, with the molecular formula glycine, N, N-diethyl-,4-(acetylamino)phenyl ester. Propacetamol is a parenteral formulation of paracetamol and thus, it is a prodrug that is completely hydrolyzed to paracetamol. It is not available in the United States but this prodrug has been widely used in other countries such as France since 1985.
Propacetamol is hydrolyzed to paracetamol and then it presents a weak inhibition of COX-1 and COX-2 which is translated into a low anti-inflammatory activity. Therefore, in high inflammatory conditions, such as rheumatoid arthritis, these agents show limited in vivo suppression of inflammation and platelet activity. The formation of N-arachidonoylphenolamine, donates paracetamol with analgesic and antipyretic properties.
| Trade Name | Propacetamol |
| Generic | Propacetamol |
| Propacetamol Other Names | Propacetamol |
| Type | |
| Formula | C14H20N2O3 |
| Weight | Average: 264.325 Monoisotopic: 264.147392512 |
| Protein binding | Propacetamol is very rapidly converted into paracetamol and this later component tends to present a very negligible binding to plasma proteins. |
| Groups | Experimental |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Propacetamol is a paracetamol prodrug of intravenous administration used to control fever and pain of perioperative period in multimodal analgesia therapy.
How Propacetamol works
As propacetamol is a prodrug, its mechanism of action is directly linked to the activity of paracetamol. The mechanism of action of paracetamol is described by the inhibition of prostaglandin synthesis. This inhibition is attained by inhibition of COX-1 and COX-2 in an environment where arachidonic acid and peroxides are kept low. It is considered that paracetamol presents a very complex mechanism of action involving effects in the peripheral system, described by direct COX inhibition; the central system, characterized by inhibition of COX, serotonergic descending neuronal pathway, L-arginine/NO pathway and cannabinoid system; and a redox mechanism. In the brain and spinal cord, paracetamol can combine with arachidonic acid to form N-arachidonoylphenolamine. This metabolite is an activator of capsaicin receptor (TRPV1) and cannabinoid CB1.
Toxicity
The intravenous administration of paracetamol in the form of propacetamol has no effect on fertility. There is no evidence of carcinogenic potential in mice but there is a report in female rats at 0.7 times the maximum clinical exposure where there was a report of mononuclear cell leukemia. There is a potential clastogenic effect at doses of 8 times the maximum anticipated clinical exposure.
Volume of Distribution
The volume of distribution of propacetamol is 1.29 l/kg.
Elimination Route
The bioavailability of 2g of propacetamol is similar to the bioavailability found in 1 g of intravenous paracetamol. Peak plasma concentration is obtained as and from the end of infusion. Pharmacokinetic analysis with intravenous propacetamol showed a significantly higher and earlier maximum plasma concentration than orally administered paracetamol. The Cmax, Tmax and AUC are 12.72 mcg/ml, 0.25 h and 25.5 mcg.h/ml. After infusion with propacetamol, significant concentrations of paracetamol are observed in cerebrospinal fluid.
Half Life
The half-life of propacetamol is of 3.6 h.
Clearance
The clearance rate of propacetamol is 0.28 l.h/kg.
Elimination Route
The metabolites of propacetamol are mainly excreted in the urine. From the elimination rate, 90% of the administered dose is excreted in 24 hours mainly as glucuronide and sulfate conjugates. Less than 5% is eliminated as unchanged paracetamol.
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