Absorption, Distribution and Excretion
Absorption occurs directly within the alveoli and enters the lung tissue. Pulmonary surfactant is distributed in the bronchi, bronchioles, and alveoli, with the highest concentration at the alveolar-air-fluid interface, where it exists as a monolayer. After 5 days, the majority of the administered dose (56%) is distributed systemically, with renal and fecal excretion being secondary clearance routes, accounting for 4% and 2% of the eliminated dose, respectively. The primary clearance route is through exhaled air, accounting for 28% of the administered dose. Cholesterol palmitate is uniformly distributed throughout all lobes of the lungs, distal airways, and alveolar spaces. In healthy lungs, it does not enter systemic circulation; however, it can enter systemic circulation when lung tissue integrity is compromised. Even 5 days after administration, 72% of the administered dose of cholesterol palmitate remains in the body, indicating that the drug has entered lipid metabolism pathways and bound to tissues. Five days after administration, 10% of the administered dose remained in the lungs and liver, while only 8% was excreted by the kidneys. This indicates extremely low renal clearance and confirms that its primary clearance route is through exhaled air. Metabolism/Metabolites: Cholesterol palmitate is catabolized and reused in lung tissue for further synthesis and secretion. Biological Half-Life: The half-life of cholesterol palmitate has been recorded as 20–36 hours.

Protein Binding

Cholesterol palmitate remains in lung tissue and is metabolized, therefore it cannot bind to plasma proteins.

1,2-Hexadecanoyl-sn-glycerol-3-phosphate choline is a phosphatidylcholine 32:0, wherein the 1- and 2-acyl groups are designated as hexadecanoyl (palmitoyl). It is a synthetic phospholipid used in liposomes and lipid bilayers for the study of biological membranes. It is also a major component of lung surfactants. It is both a surfactant and a mouse metabolite. It is a phosphatidylcholine 32:0 and also a 1-acyl-2-hexadecanoyl-sn-glycerol-3-phosphate choline. It is functionally related to hexadecanoic acid. It is the conjugate base of 1,2-di-O-palmitoyl-sn-glycerol-3-phosphate choline.
Palmitate cholinesterase is a synthetic lung surfactant used to treat infant respiratory distress syndrome. It is one of the first generation of commercially available artificial surfactants. It was developed by Burroughs Wellcome and approved by the U.S. Food and Drug Administration (FDA) on August 6, 1990. Currently, Colfosceril palmitate has entered the post-marketing withdrawal phase. It has been reported that colfosceril exists in humans (Homo sapiens), Lycoris radiata, and Trypanosoma brucei, with relevant data available. Colfosceril palmitate is a lung surfactant used to replace endogenous lung surfactant. It effectively reduces the surface tension of pulmonary fluid, thereby improving lung compliance, preventing alveolar collapse, and improving respiration. This drug is used to treat neonatal respiratory distress syndrome. PC (16:0/16:0) is a metabolite of Saccharomyces cerevisiae. Drug Indications Colfosceril palmitate is indicated for the treatment of respiratory distress syndrome (RDS) in preterm infants. Its official label states that this product is an intratracheal suspension used to prevent RDS in infants with a birth weight below 1350 grams and at risk, or to prevent RDS in infants with a birth weight above 1350 grams but with immature lung development, or for the resuscitation treatment of infants who have already developed RDS. The core characteristic of RDS is a lack of surfactant due to immature lung development. This lung disease has a high incidence, mainly attributed to risk factors such as preterm birth, maternal diabetes or male sex leading to delayed lung maturation, perinatal asphyxia, lung infection, or non-labor delivery resulting in surfactant dysfunction.

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Mechanism of Action
Treatment with cholesterol palmitate aims to re-expand collapsed lung tissue, improve lung compliance, and reduce intrapulmonary shunting. The mechanism of action of cholesterol palmitate is to reduce alveolar tension and prevent alveolar collapse by supplementing insufficient or dysfunctional endogenous surfactant. Cholesterol palmitate forms a very thin film on the surface of alveolar cells, thereby reducing surface tension.

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Pharmacodynamics
Cofaserib palmitate has been shown to significantly reduce the risk of pneumothorax, interstitial emphysema, and death. Unlike natural surfactants, cofoscelide palmitate reduces the risk of bronchopulmonary dysplasia, intraventricular hemorrhage, and patent ductus arteriosus. In placebo-controlled clinical trials, it significantly reduced the number of deaths from hyaline membrane disease, the incidence of air leakage, oxygen demand, and mean airway pressure. Some reports indicate that its efficacy may be less pronounced due to the lack of surfactant proteins.

C40H80NO8P

734.0389

733.562

63-89-8

DPPC-d9;DPPC-d62;25582-63-2;DPPC-d9-1;77165-56-1;DPPC-d4;326495-33-4;DPPC-d13;86531-55-7;DPPC-d66;326495-34-5;DPPC-d71;474943-49-2;DPPC-d75;181041-62-3

452110

White to off-white solid powder

229-229.5 °C

10.88

0

8

40

50

826

1

P(=O)([O-])(OC([H])([H])[C@@]([H])(C([H])([H])OC(C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])=O)OC(C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])=O)OC([H])([H])C([H])([H])[N+](C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H]

KILNVBDSWZSGLL-KXQOOQHDSA-N

InChI=1S/C40H80NO8P/c1-6-8-10-12-14-16-18-20-22-24-26-28-30-32-39(42)46-36-38(37-48-50(44,45)47-35-34-41(3,4)5)49-40(43)33-31-29-27-25-23-21-19-17-15-13-11-9-7-2/h38H,6-37H2,1-5H3/t38-/m1/s1

[(2R)-2,3-di(hexadecanoyloxy)propyl] 2-(trimethylazaniumyl)ethyl phosphate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

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

Ethanol : ~25 mg/mL (~34.06 mM)
DMSO :< 1 mg/mL
H2O : < 0.1 mg/mL

Solubility in Formulation 1: 2.5 mg/mL (3.41 mM) in 10% EtOH + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear EtOH 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 2: ≥ 2.5 mg/mL (3.41 mM) (saturation unknown) in 10% EtOH + 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 EtOH stock solution to 900 μL of corn oil and mix evenly.

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