Propacetamol

264.32

264.32

266-390-1

5CHW4JMR82

DTXSID3057800

C75081

N - Nervous system

2924299090

58.6

1.65

1.132 g/cm3

55-57 °C

434.5ºC at 760 mmHg

216.6ºC

1.547

H2O: soluble

UN 1282 3/PG 2

1

R11:Highly Flammable. R20/21/22:Harmful by inhalation, in contact with skin and if swallowed .

S36/37

F,Xn

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.

Propacetamol is very rapidly converted into paracetamol and this later component tends to present a very negligible binding to plasma proteins.

Propacetamol is a paracetamol prodrug of intravenous administration used to control fever and pain of perioperative period in multimodal analgesia therapy.

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.

Compounds capable of relieving pain without the loss of CONSCIOUSNESS. (See all compounds classified as Analgesics.)|Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects. (See all compounds classified as Anti-Inflammatory Agents, Non-Steroidal.)

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.|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.|The volume of distribution of propacetamol is 1.29 l/kg.|The clearance rate of propacetamol is 0.28 l.h/kg.

After administration, propacetamol is completely converted by plasma esterases into N, N-diethylglycine and paracetamol. The latest is the active metabolite. It is reported that the active metabolite of propacetamol can be transformed to N-acetil-p-benzoquinone imine by CYP2E1 which is a hepatotoxic metabolite.

The half-life of propacetamol is of 3.6 h.

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.

N, N-diethylglycine 4'-hydroxyacetanilide ester