Absorption, Distribution and Excretion
The bioavailability of 2 g of propatetamol is similar to that of 1 g of intravenously administered acetaminophen. Peak plasma concentrations are reached at the end of the infusion. Pharmacokinetic analysis of intravenously administered propatetamol showed significantly higher peak plasma concentrations than oral acetaminophen, and the time to peak concentration was also earlier. Cmax, Tmax, and AUC were 12.72 mcg/ml, 0.25 h, and 25.5 mcg·h/ml, respectively. Significant concentrations of acetaminophen were detected in the cerebrospinal fluid after propatetamol infusion. The metabolites of propatetamol are primarily excreted in the urine. Based on elimination rate, 90% of the administered dose is excreted within 24 hours primarily as glucuronide and sulfate conjugates. Less than 5% of the drug is excreted unchanged as acetaminophen. The volume of distribution of propatetamol is 1.29 L/kg.
The clearance rate of propatetamoxifen is 0.28 L/h/kg.
Metabolism/Metabolites
After administration, propatetamoxifen is completely converted to N,N-diethylglycine and acetaminophen by plasma esterases. The latter is the active metabolite. It has been reported that the active metabolite of propatetamoxifen can be converted to N-acetyl-p-benzoquinone imine via CYP2E1, which is a hepatotoxic metabolite.
Biological Half-Life
The half-life of propatetamoxifen is 3.6 hours.

Protein Binding
Propapatemol is rapidly converted to acetaminophen, which often binds very weakly to plasma proteins.

Propacetamol is an α-amino acid ester. Propacetamol is a non-opioid analgesic with no major contraindications. It is a derivative of acetaminophen (paracetamol), with the molecular formula glycine-N,N-diethyl-4-(acetamino)phenyl ester. Propacetamol is an injectable form of acetaminophen, therefore it is a prodrug that can be completely hydrolyzed to acetaminophen. It is not yet marketed in the United States, but this prodrug has been widely used in France and other countries since 1985. Propacetamol is a water-soluble para-aminophenol derivative and an ester prodrug of acetaminophen, in which acetaminophen is conjugated with diethylglycine carboxylic acid, possessing analgesic and antipyretic effects. After intravenous injection, Propacetamol is hydrolyzed to the active form acetaminophen by plasma esterases. Although acetaminophen is widely used, its exact mechanism of action is not fully understood. This drug can enter the central nervous system and exert central effects. Acetaminophen binds to cyclooxygenase (COX), preventing the metabolism of arachidonic acid into prostaglandins. Reduced prostaglandin production can relieve pain and reduce fever. Acetaminophen may also exert its central effects by acting on cannabinoid receptors and N-methyl-D-aspartate (NMDA) receptors.

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Drug Indications
Propapatemotor is a prodrug of acetaminophen used intravenously to control fever and pain in perioperative multimodal analgesia.

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Mechanism of Action
As a prodrug, propapatemotor's mechanism of action is directly related to the activity of acetaminophen. The mechanism of action of acetaminophen is through the inhibition of prostaglandin synthesis. This inhibition is achieved by inhibiting COX-1 and COX-2 in an environment of low arachidonic acid and peroxide levels. The mechanism of action of acetaminophen is highly complex, involving the peripheral system (direct inhibition of COX), the central system (inhibition of COX, serotonergic descending neural pathways, the L-arginine/NO pathway, and the endocannabinoid system), and redox mechanisms. In the brain and spinal cord, acetaminophen can bind with arachidonic acid to form N-arachidonicylphenolamine. This metabolite is an activator of the capsaicin receptor (TRPV1) and the endocannabinoid receptor CB1.

C14H20N2O3

264.3202

264.147

66532-85-2

Propacetamol hydrochloride;66532-86-3

68865

White to off-white solid powder

1.132 g/cm3

434.5ºC at 760 mmHg

216.6ºC

1.547

1.965

1

4

7

19

295

0

CCN(CC(OC1C=CC(NC(=O)C)=CC=1)=O)CC

QTGAJCQTLIRCFL-UHFFFAOYSA-N

InChI=1S/C14H20N2O3/c1-4-16(5-2)10-14(18)19-13-8-6-12(7-9-13)15-11(3)17/h6-9H,4-5,10H2,1-3H3,(H,15,17)

(4-acetamidophenyl) 2-(diethylamino)acetate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~100 mg/mL (~378.33 mM)
DMSO : ~33.33 mg/mL (~126.10 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.46 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (7.87 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (7.87 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 4: 100 mg/mL (378.33 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)